rs12600539

Variant names:

• chr17-10547499-T-C
• rs12600539
• NM_017534.6:c.324A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-10547499-T-C
• chr17-10547499-T-A
• chr17-10547499-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017534.6(MYH2):​c.324A>G​(p.Glu108Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,613,458 control chromosomes in the GnomAD database, including 162,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15308 hom., cov: 31)
  • Exomes 𝑓: 0.44 (146858 hom.)
• Consequence: MYH2 NM_017534.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 3.39
• Publications: 18 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 17-10547499-T-C is Benign according to our data. Variant chr17-10547499-T-C is described in ClinVar as Benign. ClinVar VariationId is 260821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 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.324A>G	p.Glu108Glu	synonymous	Exon 4 of 40	NP_060004.3
	MYH2	NM_001100112.2		c.324A>G	p.Glu108Glu	synonymous	Exon 4 of 40	NP_001093582.1	Q9UKX2-1
	MYHAS	NR_125367.1		n.168-20038T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH2	ENST00000245503.10	TSL:1 MANE Select	c.324A>G	p.Glu108Glu	synonymous	Exon 4 of 40	ENSP00000245503.5	Q9UKX2-1
	MYH2	ENST00000532183.6	TSL:1	c.324A>G	p.Glu108Glu	synonymous	Exon 3 of 17	ENSP00000433944.1	Q9UKX2-2
	MYH2	ENST00000622564.4	TSL:1	c.324A>G	p.Glu108Glu	synonymous	Exon 4 of 18	ENSP00000482463.1	Q9UKX2-2

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66537 AN: 151796 Hom.: 15291 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.429

GnomAD2 exomes AF: 0.498 AC: 125230 AN: 251368 AF XY: 0.496

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.613

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.867

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.438 AC: 640398 AN: 1461542 Hom.: 146858 Cov.: 57 AF XY: 0.442 AC XY: 321338 AN XY: 727106

African (AFR) AF: 0.379 AC: 12696 AN: 33472

American (AMR) AF: 0.597 AC: 26677 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11871 AN: 26134

East Asian (EAS) AF: 0.840 AC: 33340 AN: 39700

South Asian (SAS) AF: 0.596 AC: 51442 AN: 86252

European-Finnish (FIN) AF: 0.438 AC: 23409 AN: 53420

Middle Eastern (MID) AF: 0.460 AC: 2652 AN: 5764

European-Non Finnish (NFE) AF: 0.406 AC: 451318 AN: 1111698

Other (OTH) AF: 0.447 AC: 26993 AN: 60382

GnomAD4 genome AF: 0.438 AC: 66605 AN: 151916 Hom.: 15308 Cov.: 31 AF XY: 0.449 AC XY: 33329 AN XY: 74194

African (AFR) AF: 0.388 AC: 16067 AN: 41408

American (AMR) AF: 0.500 AC: 7637 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1554 AN: 3464

East Asian (EAS) AF: 0.850 AC: 4377 AN: 5148

South Asian (SAS) AF: 0.620 AC: 2980 AN: 4810

European-Finnish (FIN) AF: 0.450 AC: 4746 AN: 10536

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27785 AN: 67960

Other (OTH) AF: 0.429 AC: 905 AN: 2112

Alfa AF: 0.419 Hom.: 6198

Bravo AF: 0.438

Asia WGS AF: 0.675 AC: 2343 AN: 3478

EpiCase AF: 0.408

EpiControl AF: 0.413

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		3.4
PromoterAI		-0.015	Neutral
Mutation Taster		=85/15	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: rs12600539; hg19: chr17-10450816; COSMIC: COSV55434394;