8-2153148-C-T

Variant names:

• chr8-2153148-C-T
• rs11987927
• ENST00000520779.1:n.154+9692C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520779.1(MYOM2):​n.154+9692C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 150,418 control chromosomes in the GnomAD database, including 1,800 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1800 hom., cov: 32)
• Consequence: MYOM2 ENST00000520779.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM2	ENST00000520779.1	n.154+9692C>T		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18066 AN: 150362 Hom.: 1793 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0982

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 18097 AN: 150418 Hom.: 1800 Cov.: 32 AF XY: 0.123 AC XY: 9037 AN XY: 73308

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0384

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.0988

Alfa AF: 0.0490 Hom.: 512

Bravo AF: 0.133

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11987927; hg19: chr8-2101074;