chr14-23389062-AGG-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_002471.4(MYH6):c.3979-9_3979-8delCC 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 Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 763 hom., cov: 0)

Exomes 𝑓: 0.14 ( 11301 hom. )

Failed GnomAD Quality Control

Consequence

MYH6
NM_002471.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 14-23389062-AGG-A is Benign according to our data. Variant chr14-23389062-AGG-A is described in ClinVar as [Benign]. Clinvar id is 220788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23389062-AGG-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH6	NM_002471.4 link	c.3979-9_3979-8delCC		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.3979-9_3979-8delCC		splice_region_variant, intron_variant	Intron 28 of 38	5	NM_002471.4	ENSP00000386041.3		P13533

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

14951

AN:

115620

Hom.:

761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0912

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.000657

Gnomad SAS

AF:

0.0461

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.0969

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.121

GnomAD2 exomes

AF:

0.122

AC:

17018

AN:

139674

AF XY:

0.120

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.0826

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.000548

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.141

AC:

149380

AN:

1057912

Hom.:

11301

AF XY:

0.137

AC XY:

72412

AN XY:

527248

show subpopulations

African (AFR)

AF:

0.112

AC:

3379

AN:

30300

American (AMR)

AF:

0.0667

AC:

1970

AN:

29532

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

3486

AN:

19368

East Asian (EAS)

AF:

0.000180

AC:

AN:

27780

South Asian (SAS)

AF:

0.0497

AC:

3254

AN:

65464

European-Finnish (FIN)

AF:

0.107

AC:

3761

AN:

35006

Middle Eastern (MID)

AF:

0.0937

AC:

393

AN:

4194

European-Non Finnish (NFE)

AF:

0.159

AC:

127150

AN:

801160

Other (OTH)

AF:

0.133

AC:

5982

AN:

45108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.629

Heterozygous variant carriers

3836

7673

11509

15346

19182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.129

AC:

14958

AN:

115736

Hom.:

763

Cov.:

AF XY:

0.125

AC XY:

7118

AN XY:

56878

show subpopulations

African (AFR)

AF:

0.109

AC:

4258

AN:

38888

American (AMR)

AF:

0.0912

AC:

1030

AN:

11288

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

505

AN:

2596

East Asian (EAS)

AF:

0.000659

AC:

AN:

3034

South Asian (SAS)

AF:

0.0460

AC:

158

AN:

3432

European-Finnish (FIN)

AF:

0.122

AC:

863

AN:

7100

Middle Eastern (MID)

AF:

0.0992

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.167

AC:

7846

AN:

46890

Other (OTH)

AF:

0.119

AC:

190

AN:

1590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.551

Heterozygous variant carriers

629

1259

1888

2518

3147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Aug 16, 2019

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus 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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Cardiomyopathy

Benign:1

Mar 08, 2018

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

Loading publications...

chr14-23389062-AGG-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over