rs7223755

Variant names:

• chr17-10523026-C-T
• rs7223755
• NM_017534.6:c.5673+64G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017534.6(MYH2):​c.5673+64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,159,706 control chromosomes in the GnomAD database, including 182,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20850 hom., cov: 33)
  • Exomes 𝑓: 0.56 (161493 hom.)
• Consequence: MYH2 NM_017534.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0890
• Publications: 6 publications found

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]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-10523026-C-T is Benign according to our data. Variant chr17-10523026-C-T is described in ClinVar as Benign. ClinVar VariationId is 1260946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH2	NM_017534.6	c.5673+64G>A		intron_variant	Intron 39 of 39	ENST00000245503.10	NP_060004.3
MYH2	NM_001100112.2	c.5673+64G>A		intron_variant	Intron 39 of 39		NP_001093582.1
MYHAS	NR_125367.1	n.168-44511C>T		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10	c.5673+64G>A		intron_variant	Intron 39 of 39	1	NM_017534.6	ENSP00000245503.5

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78046 AN: 151866 Hom.: 20834 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.557 AC: 561634 AN: 1007722 Hom.: 161493 AF XY: 0.555 AC XY: 288807 AN XY: 520380

African (AFR) AF: 0.420 AC: 10153 AN: 24146

American (AMR) AF: 0.403 AC: 17080 AN: 42332

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 13257 AN: 23296

East Asian (EAS) AF: 0.200 AC: 7415 AN: 37096

South Asian (SAS) AF: 0.438 AC: 33111 AN: 75514

European-Finnish (FIN) AF: 0.589 AC: 30815 AN: 52352

Middle Eastern (MID) AF: 0.444 AC: 1780 AN: 4012

European-Non Finnish (NFE) AF: 0.602 AC: 423407 AN: 703886

Other (OTH) AF: 0.546 AC: 24616 AN: 45088

GnomAD4 genome AF: 0.514 AC: 78114 AN: 151984 Hom.: 20850 Cov.: 33 AF XY: 0.507 AC XY: 37687 AN XY: 74278

African (AFR) AF: 0.424 AC: 17548 AN: 41430

American (AMR) AF: 0.464 AC: 7103 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3470

East Asian (EAS) AF: 0.193 AC: 997 AN: 5164

South Asian (SAS) AF: 0.428 AC: 2059 AN: 4812

European-Finnish (FIN) AF: 0.583 AC: 6141 AN: 10542

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.598 AC: 40633 AN: 67964

Other (OTH) AF: 0.523 AC: 1104 AN: 2110

Alfa AF: 0.543 Hom.: 3454

Bravo AF: 0.501

Asia WGS AF: 0.373 AC: 1302 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.24
PhyloP100		0.089
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7223755; hg19: chr17-10426343;