Variant chr14-23389062-AG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_002471.4(MYH6):c.3979-8delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.35 ( 8254 hom., cov: 0)

Exomes 𝑓: 0.31 ( 26611 hom. )

Failed GnomAD Quality Control

Consequence

MYH6
NM_002471.4 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:8O:2

Conservation

PhyloP100: 0.275

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 14-23389062-AG-A is Benign according to our data. Variant chr14-23389062-AG-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 36628.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Benign=4, Likely_benign=2, not_provided=2}. Variant chr14-23389062-AG-A is described in Lovd as [Benign]. Variant chr14-23389062-AG-A is described in Lovd as [Benign]. Variant chr14-23389062-AG-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH6	NM_002471.4 link	c.3979-8delC		splice_region_variant, intron_variant	Intron 28 of 38	ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9 link	c.3979-8delC		splice_region_variant, intron_variant	Intron 28 of 38	5	NM_002471.4	ENSP00000386041.3		P13533

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

40782

AN:

115534

Hom.:

8236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.260

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.338

GnomAD3 exomes

AF:

0.320

AC:

44689

AN:

139674

Hom.:

4831

AF XY:

0.320

AC XY:

24389

AN XY:

76278

show subpopulations

Gnomad AFR exome

AF:

0.610

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.283

Gnomad EAS exome

AF:

0.271

Gnomad SAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.283

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.308

AC:

297903

AN:

966060

Hom.:

26611

Cov.:

AF XY:

0.307

AC XY:

147489

AN XY:

479754

show subpopulations

Gnomad4 AFR exome

AF:

0.616

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.260

Gnomad4 SAS exome

AF:

0.350

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.323

GnomAD4 genome

AF:

0.353

AC:

40854

AN:

115646

Hom.:

8254

Cov.:

AF XY:

0.345

AC XY:

19621

AN XY:

56834

show subpopulations

Gnomad4 AFR

AF:

0.612

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.157

Gnomad4 SAS

AF:

0.317

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.337

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:8Other:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:4Other:1

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 08, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
not provided, no classification provided	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 09, 2014	- -

Cardiomyopathy

Benign:2

Benign, criteria provided, single submitter	clinical testing	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	Apr 04, 2016	- -
Likely benign, criteria provided, single submitter	curation	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 18, 2011	- -

Dilated Cardiomyopathy, Dominant

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Atrial septal defect

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hypertrophic cardiomyopathy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hypertrophic cardiomyopathy 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 04, 2025

- -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2015

This alteration is classified as likely 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. -

Hypertrophic cardiomyopathy 2

Other:1

not provided, no classification provided

clinical testing

Institute of Human Genetics, University of Wuerzburg

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over