rs382872

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002471.4(MYH6):​c.4980C>T​(p.Asp1660Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,614,156 control chromosomes in the GnomAD database, including 9,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 539 hom., cov: 31)
Exomes 𝑓: 0.10 ( 8687 hom. )

Consequence

MYH6
NM_002471.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.151

Publications

14 publications found
Variant links:
Genes affected
MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]
MYH6 Gene-Disease associations (from GenCC):
  • hypertrophic cardiomyopathy 14
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine
  • Keppen-Lubinsky syndrome
    Inheritance: AD Classification: MODERATE Submitted by: Illumina
  • familial isolated dilated cardiomyopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • atrial septal defect 3
    Inheritance: AD Classification: LIMITED Submitted by: G2P
  • dilated cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • hypertrophic cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 14-23386111-G-A is Benign according to our data. Variant chr14-23386111-G-A is described in ClinVar as [Benign]. Clinvar id is 44528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.151 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYH6NM_002471.4 linkc.4980C>T p.Asp1660Asp synonymous_variant Exon 34 of 39 ENST00000405093.9 NP_002462.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYH6ENST00000405093.9 linkc.4980C>T p.Asp1660Asp synonymous_variant Exon 34 of 39 5 NM_002471.4 ENSP00000386041.3 P13533

Frequencies

GnomAD3 genomes
AF:
0.0761
AC:
11578
AN:
152152
Hom.:
538
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0310
Gnomad AMI
AF:
0.0899
Gnomad AMR
AF:
0.0546
Gnomad ASJ
AF:
0.124
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0317
Gnomad FIN
AF:
0.0902
Gnomad MID
AF:
0.0696
Gnomad NFE
AF:
0.113
Gnomad OTH
AF:
0.0721
GnomAD2 exomes
AF:
0.0754
AC:
18958
AN:
251326
AF XY:
0.0759
show subpopulations
Gnomad AFR exome
AF:
0.0300
Gnomad AMR exome
AF:
0.0356
Gnomad ASJ exome
AF:
0.130
Gnomad EAS exome
AF:
0.000272
Gnomad FIN exome
AF:
0.0859
Gnomad NFE exome
AF:
0.108
Gnomad OTH exome
AF:
0.0901
GnomAD4 exome
AF:
0.103
AC:
149850
AN:
1461886
Hom.:
8687
Cov.:
35
AF XY:
0.101
AC XY:
73280
AN XY:
727242
show subpopulations
African (AFR)
AF:
0.0271
AC:
908
AN:
33480
American (AMR)
AF:
0.0374
AC:
1672
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.130
AC:
3393
AN:
26136
East Asian (EAS)
AF:
0.000176
AC:
7
AN:
39700
South Asian (SAS)
AF:
0.0395
AC:
3406
AN:
86258
European-Finnish (FIN)
AF:
0.0841
AC:
4493
AN:
53418
Middle Eastern (MID)
AF:
0.0730
AC:
421
AN:
5768
European-Non Finnish (NFE)
AF:
0.117
AC:
129697
AN:
1112006
Other (OTH)
AF:
0.0969
AC:
5853
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
10004
20008
30012
40016
50020
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4600
9200
13800
18400
23000
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0761
AC:
11581
AN:
152270
Hom.:
539
Cov.:
31
AF XY:
0.0746
AC XY:
5553
AN XY:
74438
show subpopulations
African (AFR)
AF:
0.0310
AC:
1290
AN:
41564
American (AMR)
AF:
0.0546
AC:
836
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.124
AC:
429
AN:
3468
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5176
South Asian (SAS)
AF:
0.0317
AC:
153
AN:
4826
European-Finnish (FIN)
AF:
0.0902
AC:
956
AN:
10602
Middle Eastern (MID)
AF:
0.0714
AC:
21
AN:
294
European-Non Finnish (NFE)
AF:
0.113
AC:
7662
AN:
68008
Other (OTH)
AF:
0.0714
AC:
151
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
562
1124
1687
2249
2811
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
132
264
396
528
660
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0955
Hom.:
475
Bravo
AF:
0.0727
Asia WGS
AF:
0.0180
AC:
63
AN:
3478
EpiCase
AF:
0.108
EpiControl
AF:
0.109

ClinVar

Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Sep 27, 2011
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Clinical Genetics, Academic Medical Center
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy 14 Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Cardiovascular phenotype Benign:1
Jun 15, 2015
Ambry Genetics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.10
DANN
Benign
0.88
PhyloP100
-0.15
Mutation Taster
=96/4
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs382872; hg19: chr14-23855320; COSMIC: COSV108192357; COSMIC: COSV108192357; API