DSC2 : c.2326A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.2326A>G	p.I776V (Ile > Val)	substitution	missense	chr18:28649042 (reverse strand)	0.11900915

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.11900915 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

DCM	OMGL: Detected in 0 / 304 DCM patients. LMM: Detected in 0 / 123 DCM patients.
ARVC	OMGL: Detected in 0 / 351 ARVC patients sequenced at OMGL.

DCM

OMGL: Detected in 0 / 304 DCM patients.

LMM: Detected in 0 / 123 DCM patients.

ARVC

OMGL: Detected in 0 / 351 ARVC patients sequenced at OMGL.

For more information on the clinical significance of this variant, please see the ClinVar entry.

Detection in Population Databases

Database	European	African	East Asian	South Asian	American	Finnish	Other	Total
ExAC	0.08418559 5614 / 66686	0.41959992 4363 / 10398	0.09675926 836 / 8640	0.06540698 1080 / 16512	0.17840457 2062 / 11558	0.05930408 392 / 6610	0.09933775 90 / 906	0.11900915 14437 / 121310
ESP	0.08372 720 / 8600	0.40104 1767 / 4406						0.19122 2487 / 13006
1KG	0.09901 80 / 808	0.47201 624 / 1322	0.07837 79 / 1008	0.05828 57 / 978	0.17867 124 / 694	0.10101 20 / 198		0.19649 984 / 5008

View sub-population details for 1000 Genomes (1KG) data

Hide sub-population details for 1000 Genomes (1KG) data

0.13187 24 / 182 British	0.44262 54 / 122 African-American	0.06452 12 / 186 Chinese Dai	0.06977 12 / 172 Bengali	0.17553 33 / 188 Colombian
0.07944 17 / 214 Iberian	0.43229 83 / 192 African-Caribbean	0.11165 23 / 206 Han, Beijing	0.05825 12 / 206 Gujarati Indian	0.17969 23 / 128 Mexican, LA
0.07009 15 / 214 Toscani	0.45455 90 / 198 Esan, Nigeria	0.07212 15 / 208 Japanese	0.03922 8 / 204 Indian Telugu	0.18824 32 / 170 Peruvian
0.12121 24 / 198 Utah Europeans	0.49558 112 / 226 Gambian	0.07071 14 / 198 Kinh, Vietnam	0.06771 13 / 192 Punjabi, Lahore	0.17308 36 / 208 Puerto Rican
	0.51010 101 / 198 Luhya, Kenya	0.07143 15 / 210 Southern Han	0.05882 12 / 204 Tamil
	0.52941 90 / 170 Mende
	0.43519 94 / 216 Yoruba, Nigeria

The Exome Aggregation Consortium (ExAC) is a database of 60,706 unrelated individuals sequenced as part of various disease-specific and population genetic studies. There is partial overlap between ExAC and 1000 Genomes (1KG) (1,851 of the 2,504 samples in 1KG) and the Exome Sequencing Project (ESP) (3,936 of the 6,500 samples in ESP).

Other Variant & Gene Details

Canonical Sequences
Transcript	ENST00000280904	LRG_400t2	NM_024422.3
Protein	ENSP00000280904	LRG_400p2		Q02487

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 0% of algorithms have predicted that this variant will adversely affect protein function
tolerated	conservative	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	polymorphism (auto)	neutral	tolerated

References

1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.

2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.

3. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015 Nov;17(11):880-8.