chr17-10542865-C-T

Variant names:

• chr17-10542865-C-T
• rs719277
• NM_017534.6:c.904+10G>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.904+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,539,660 control chromosomes in the GnomAD database, including 148,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13798 hom., cov: 33)
  • Exomes 𝑓: 0.43 (134908 hom.)
• Consequence: MYH2 NM_017534.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.929
• Publications: 10 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=-0.85).
• BP6: Variant 17-10542865-C-T is Benign according to our data. Variant chr17-10542865-C-T is described in ClinVar as Benign. ClinVar VariationId is 260829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017534.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH2	NM_017534.6	MANE Select	c.904+10G>A		intron	N/A	NP_060004.3
	MYH2	NM_001100112.2		c.904+10G>A		intron	N/A	NP_001093582.1	Q9UKX2-1
	MYHAS	NR_125367.1		n.168-24672C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH2	ENST00000245503.10	TSL:1 MANE Select	c.904+10G>A		intron	N/A	ENSP00000245503.5	Q9UKX2-1
	MYH2	ENST00000532183.6	TSL:1	c.904+10G>A		intron	N/A	ENSP00000433944.1	Q9UKX2-2
	MYH2	ENST00000622564.4	TSL:1	c.904+10G>A		intron	N/A	ENSP00000482463.1	Q9UKX2-2

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62530 AN: 151876 Hom.: 13786 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.410

GnomAD2 exomes AF: 0.486 AC: 119756 AN: 246534 AF XY: 0.485

Gnomad AFR exome AF: 0.301

Gnomad AMR exome AF: 0.598

Gnomad ASJ exome AF: 0.452

Gnomad EAS exome AF: 0.848

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.402

Gnomad OTH exome AF: 0.442

GnomAD4 exome AF: 0.429 AC: 595951 AN: 1387666 Hom.: 134908 Cov.: 24 AF XY: 0.434 AC XY: 301360 AN XY: 694496

African (AFR) AF: 0.298 AC: 9504 AN: 31912

American (AMR) AF: 0.583 AC: 25820 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 11583 AN: 25632

East Asian (EAS) AF: 0.830 AC: 32425 AN: 39062

South Asian (SAS) AF: 0.593 AC: 49979 AN: 84266

European-Finnish (FIN) AF: 0.438 AC: 23259 AN: 53134

Middle Eastern (MID) AF: 0.453 AC: 2492 AN: 5504

European-Non Finnish (NFE) AF: 0.397 AC: 415676 AN: 1045970

Other (OTH) AF: 0.436 AC: 25213 AN: 57874

GnomAD4 genome AF: 0.412 AC: 62583 AN: 151994 Hom.: 13798 Cov.: 33 AF XY: 0.424 AC XY: 31486 AN XY: 74284

African (AFR) AF: 0.307 AC: 12711 AN: 41448

American (AMR) AF: 0.488 AC: 7461 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3466

East Asian (EAS) AF: 0.834 AC: 4328 AN: 5188

South Asian (SAS) AF: 0.616 AC: 2972 AN: 4824

European-Finnish (FIN) AF: 0.452 AC: 4757 AN: 10530

Middle Eastern (MID) AF: 0.445 AC: 129 AN: 290

European-Non Finnish (NFE) AF: 0.403 AC: 27395 AN: 67942

Other (OTH) AF: 0.408 AC: 863 AN: 2114

Alfa AF: 0.407 Hom.: 16959

Bravo AF: 0.407

Asia WGS AF: 0.652 AC: 2259 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Myopathy, proximal, and ophthalmoplegia (4)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.90
DANN	Benign	0.54
PhyloP100		-0.93
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: rs719277; hg19: chr17-10446182; COSMIC: COSV55450958; COSMIC: COSV55450958;