NM_002471.4:c.5164-22A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002471.4(MYH6):c.5164-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 1,613,572 control chromosomes in the GnomAD database, including 5,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.078 ( 526 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5298 hom. )

Consequence

MYH6
NM_002471.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.698

Publications

12 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

MYH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 14-23385063-T-C is Benign according to our data. Variant chr14-23385063-T-C is described in ClinVar as Benign. ClinVar VariationId is 258713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH6	NM_002471.4 link	c.5164-22A>G		intron_variant	Intron 34 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.5164-22A>G		intron_variant	Intron 34 of 38	5	NM_002471.4	ENSP00000386041.3		P13533

Frequencies

GnomAD3 genomes

AF:

0.0779

AC:

11836

AN:

152016

Hom.:

528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0615

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0557

Gnomad ASJ

AF:

0.0729

Gnomad EAS

AF:

0.0637

Gnomad SAS

AF:

0.0778

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0811

Gnomad OTH

AF:

0.0742

GnomAD2 exomes

AF:

0.0793

AC:

19936

AN:

251448

AF XY:

0.0805

show subpopulations

Gnomad AFR exome

AF:

0.0636

Gnomad AMR exome

AF:

0.0296

Gnomad ASJ exome

AF:

0.0702

Gnomad EAS exome

AF:

0.0624

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.0831

Gnomad OTH exome

AF:

0.0776

GnomAD4 exome

AF:

0.0811

AC:

118582

AN:

1461438

Hom.:

5298

Cov.:

AF XY:

0.0815

AC XY:

59254

AN XY:

727072

show subpopulations

African (AFR)

AF:

0.0609

AC:

2039

AN:

33470

American (AMR)

AF:

0.0321

AC:

1436

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0698

AC:

1825

AN:

26132

East Asian (EAS)

AF:

0.0850

AC:

3374

AN:

39690

South Asian (SAS)

AF:

0.0797

AC:

6877

AN:

86250

European-Finnish (FIN)

AF:

0.159

AC:

8495

AN:

53376

Middle Eastern (MID)

AF:

0.0581

AC:

335

AN:

5768

European-Non Finnish (NFE)

AF:

0.0805

AC:

89450

AN:

1111654

Other (OTH)

AF:

0.0787

AC:

4751

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

5429

10858

16286

21715

27144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3324

6648

9972

13296

16620

<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:

0.0777

AC:

11824

AN:

152134

Hom.:

526

Cov.:

AF XY:

0.0810

AC XY:

6022

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0612

AC:

2542

AN:

41522

American (AMR)

AF:

0.0555

AC:

848

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0729

AC:

253

AN:

3470

East Asian (EAS)

AF:

0.0638

AC:

328

AN:

5140

South Asian (SAS)

AF:

0.0771

AC:

372

AN:

4826

European-Finnish (FIN)

AF:

0.168

AC:

1782

AN:

10578

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0811

AC:

5513

AN:

68004

Other (OTH)

AF:

0.0729

AC:

154

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

561

1123

1684

2246

2807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0768

Hom.:

961

Bravo

AF:

0.0683

Asia WGS

AF:

0.0760

AC:

264

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.58

PhyloP100

-0.70

BranchPoint Hunter

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over