Variant rs2277652 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017534.6(MYH2):c.3117+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,614,102 control chromosomes in the GnomAD database, including 3,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 350 hom., cov: 32)

Exomes 𝑓: 0.059 ( 2916 hom. )

Consequence

MYH2
NM_017534.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00700

Variant links:

Genes affected

MYH2 (HGNC:7572): (myosin heavy chain 2) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in inclusion body myopathy-3. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]

MYH2 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-10529532-G-A is Benign according to our data. Variant chr17-10529532-G-A is described in ClinVar as [Benign]. Clinvar id is 260820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MYH2	NM_017534.6 linkuse as main transcript	c.3117+32C>T	intron_variant	ENST00000245503.10
MYHAS	NR_125367.1 linkuse as main transcript	n.168-38005G>A	intron_variant, non_coding_transcript_variant
MYH2	NM_001100112.2 linkuse as main transcript	c.3117+32C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH2	ENST00000245503.10 linkuse as main transcript	c.3117+32C>T		intron_variant		1	NM_017534.6	P1	Q9UKX2-1
	ENST00000399342.6 linkuse as main transcript	n.207-3792G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0634

AC:

9648

AN:

152098

Hom.:

342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0798

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0460

Gnomad ASJ

AF:

0.0787

Gnomad EAS

AF:

0.0284

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.0527

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0565

Gnomad OTH

AF:

0.0740

GnomAD3 exomes

AF:

0.0598

AC:

15041

AN:

251448

Hom.:

578

AF XY:

0.0629

AC XY:

8553

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0821

Gnomad AMR exome

AF:

0.0370

Gnomad ASJ exome

AF:

0.0815

Gnomad EAS exome

AF:

0.0226

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0544

Gnomad NFE exome

AF:

0.0549

Gnomad OTH exome

AF:

0.0572

GnomAD4 exome

AF:

0.0589

AC:

86036

AN:

1461888

Hom.:

2916

Cov.:

AF XY:

0.0604

AC XY:

43952

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0824

Gnomad4 AMR exome

AF:

0.0382

Gnomad4 ASJ exome

AF:

0.0816

Gnomad4 EAS exome

AF:

0.0284

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.0537

Gnomad4 NFE exome

AF:

0.0556

Gnomad4 OTH exome

AF:

0.0623

GnomAD4 genome

AF:

0.0637

AC:

9690

AN:

152214

Hom.:

350

Cov.:

AF XY:

0.0646

AC XY:

4809

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0806

Gnomad4 AMR

AF:

0.0460

Gnomad4 ASJ

AF:

0.0787

Gnomad4 EAS

AF:

0.0285

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.0527

Gnomad4 NFE

AF:

0.0565

Gnomad4 OTH

AF:

0.0728

Alfa

AF:

0.0585

Hom.:

Bravo

AF:

0.0619

Asia WGS

AF:

0.0780

AC:

271

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.48

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