rs2277652

chr17-10529532-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00700

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]

(HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH2	NM_017534.6	c.3117+32C>T		intron_variant		ENST00000245503.10
MYHAS	NR_125367.1	n.168-38005G>A		intron_variant, non_coding_transcript_variant
MYH2	NM_001100112.2	c.3117+32C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9648 AN: 152098 Hom.: 342 Cov.: 32

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

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.: 35 AF XY: 0.0604 AC XY: 43952 AN XY: 727244

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.: 32 AF XY: 0.0646 AC XY: 4809 AN XY: 74402

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.: 38

Bravo AF: 0.0619

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	11
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

Other links and lift over

dbSNP: rs2277652; hg19: chr17-10432849; COSMIC: COSV55439170;