9-35683244-G-GGC

Position:

• chr9-35683244-G-GGC

Variant summary

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

The NM_003289.4(TPM2):​c.773-4_773-3insGC variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TPM2 NM_003289.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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 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/exons	MANE	Protein	UniProt
TPM2	NM_003289.4	c.773-4_773-3insGC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000645482.3	NP_003280.2
TPM2	NM_001301226.2	c.772+1001_772+1002insGC		intron_variant			NP_001288155.1
TPM2	NM_001301227.2	c.773-4_773-3insGC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001288156.1
TPM2	NM_213674.1	c.772+1001_772+1002insGC		intron_variant			NP_998839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPM2	ENST00000645482.3	c.773-4_773-3insGC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_003289.4	ENSP00000496494	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886063905; hg19: chr9-35683241;