rs1998308

Variant names:

• chr9-35683885-A-T
• rs1998308
• NM_003289.4:c.772+361T>A

Variant summary

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

The NM_003289.4(TPM2):​c.772+361T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,062 control chromosomes in the GnomAD database, including 27,602 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 0.60 (27602 hom., cov: 32)
• Consequence: TPM2 NM_003289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

Genes affected

TPM2 (HGNC:12011): (tropomyosin 2) This gene encodes beta-tropomyosin, a member of the actin filament binding protein family, and mainly expressed in slow, type 1 muscle fibers. Mutations in this gene can alter the expression of other sarcomeric tropomyosin proteins, and cause cap disease, nemaline myopathy and distal arthrogryposis syndromes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPM2	NM_003289.4	c.772+361T>A		intron_variant	Intron 8 of 8	ENST00000645482.3	NP_003280.2
TPM2	NM_001301226.2	c.772+361T>A		intron_variant	Intron 8 of 8		NP_001288155.1
TPM2	NM_001301227.2	c.772+361T>A		intron_variant	Intron 8 of 8		NP_001288156.1
TPM2	NM_213674.1	c.772+361T>A		intron_variant	Intron 8 of 8		NP_998839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPM2	ENST00000645482.3	c.772+361T>A		intron_variant	Intron 8 of 8		NM_003289.4	ENSP00000496494.2

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90800 AN: 151944 Hom.: 27566 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.598 AC: 90882 AN: 152062 Hom.: 27602 Cov.: 32 AF XY: 0.593 AC XY: 44048 AN XY: 74340

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.595

Alfa AF: 0.622 Hom.: 3655

Bravo AF: 0.602

Asia WGS AF: 0.467 AC: 1626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs1998308; hg19: chr9-35683882; COSMIC: COSV61406040; COSMIC: COSV61406040;