rs1243872

Positions:

• chr9-35686410-T-G

Variant summary

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

The NM_003289.4(TPM2):​c.241-630A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 158,826 control chromosomes in the GnomAD database, including 18,842 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 0.49 (18149 hom., cov: 30)
  • Exomes 𝑓: 0.44 (693 hom.)
• Consequence: TPM2 NM_003289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPM2	NM_003289.4	c.241-630A>C		intron_variant		ENST00000645482.3	NP_003280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPM2	ENST00000645482.3	c.241-630A>C		intron_variant			NM_003289.4	ENSP00000496494	A1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73965 AN: 151814 Hom.: 18129 Cov.: 30

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.436 AC: 3007 AN: 6894 Hom.: 693 Cov.: 0 AF XY: 0.432 AC XY: 1574 AN XY: 3646

Gnomad4 AFR exome AF: 0.542

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.554

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.453

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.487 AC: 74026 AN: 151932 Hom.: 18149 Cov.: 30 AF XY: 0.486 AC XY: 36122 AN XY: 74268

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.502

Alfa AF: 0.469 Hom.: 10965

Bravo AF: 0.491

Asia WGS AF: 0.555 AC: 1929 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.78

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: rs1243872; hg19: chr9-35686407;