8-2052262-G-C

Variant names:

• chr8-2052262-G-C
• rs763164767
• NM_003970.4:c.212G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003970.4(MYOM2):​c.212G>C​(p.Cys71Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,459,448 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: MYOM2 NM_003970.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.72

Genes affected

MYOM2 (HGNC:7614): (myomesin 2) The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD and 165 kD. The predicted MYOM2 protein contains 1,465 amino acids. Like MYOM1, MYOM2 has a unique N-terminal domain followed by 12 repeat domains with strong homology to either fibronectin type III or immunoglobulin C2 domains. Protein sequence comparisons suggested that the MYOM2 protein and bovine M protein are identical. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM2	NM_003970.4	c.212G>C	p.Cys71Ser	missense_variant	Exon 3 of 37	ENST00000262113.9	NP_003961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM2	ENST00000262113.9	c.212G>C	p.Cys71Ser	missense_variant	Exon 3 of 37	1	NM_003970.4	ENSP00000262113.4
MYOM2	ENST00000523438.1	c.-82+7094G>C		intron_variant	Intron 1 of 23	2		ENSP00000428396.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 249284 Hom.: 0 AF XY: 0.0000223 AC XY: 3 AN XY: 134720

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000994

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459448 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 725978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000700

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	17
DANN	Benign	0.55
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.19
Sift	Benign	0.92	T
Sift4G	Benign	0.57	T
Vest4		0.75
MutPred		0.36		Gain of sheet (P = 4e-04);
MVP		0.55
MPC		0.0075
ClinPred		0.14	T
GERP RS		4.7
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs763164767; hg19: chr8-2000380;