9-35682882-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000378292.9(TPM2):c.773-719G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000685 in 1,465,118 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (1 hom.)
• Consequence: TPM2 ENST00000378292.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.105

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-35682882-C-T is Benign according to our data. Variant chr9-35682882-C-T is described in ClinVar as [Benign]. Clinvar id is 1879734.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 107 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPM2	NM_001301226.2	c.773-719G>A		intron_variant
TPM2	NM_213674.1	c.773-719G>A		intron_variant
TPM2	NM_003289.4			downstream_gene_variant		ENST00000645482.3
TPM2	NM_001301227.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPM2	ENST00000645482.3			downstream_gene_variant			NM_003289.4	A1

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152114 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000659 AC: 89 AN: 135044 Hom.: 0 AF XY: 0.000729 AC XY: 52 AN XY: 71344

Gnomad AFR exome AF: 0.000425

Gnomad AMR exome AF: 0.000171

Gnomad ASJ exome AF: 0.00222

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000156

Gnomad FIN exome AF: 0.000495

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.000255

GnomAD4 exome AF: 0.000683 AC: 897 AN: 1313004 Hom.: 1 Cov.: 32 AF XY: 0.000702 AC XY: 452 AN XY: 644016

Gnomad4 AFR exome AF: 0.0000669

Gnomad4 AMR exome AF: 0.000186

Gnomad4 ASJ exome AF: 0.00166

Gnomad4 EAS exome AF: 0.0000336

Gnomad4 SAS exome AF: 0.0000933

Gnomad4 FIN exome AF: 0.000293

Gnomad4 NFE exome AF: 0.000795

Gnomad4 OTH exome AF: 0.000340

GnomAD4 genome AF: 0.000703 AC: 107 AN: 152114 Hom.: 0 Cov.: 33 AF XY: 0.000619 AC XY: 46 AN XY: 74292

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000655

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000661

Gnomad4 NFE AF: 0.00118

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.000612

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

TPM2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.9
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs776727318; hg19: chr9-35682879;