Variant 9-35683243-T-TGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_003289.4(TPM2):c.773-4_773-3dupCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 1,472,824 control chromosomes in the GnomAD database, including 899 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 770 hom., cov: 0)

Exomes 𝑓: 0.035 ( 129 hom. )

Consequence

TPM2
NM_003289.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.23

Variant links:

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]

TPM2 links:

TPM2 (HGNC:):

TPM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-35683243-T-TGG is Benign according to our data. Variant chr9-35683243-T-TGG is described in ClinVar as [Likely_benign]. Clinvar id is 94125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TPM2	NM_003289.4 linkuse as main transcript	c.773-4_773-3dupCC	splice_region_variant, intron_variant	ENST00000645482.3	NP_003280.2	P07951-1
TPM2	NM_001301226.2 linkuse as main transcript	c.772+1001_772+1002dupCC	intron_variant		NP_001288155.1	Q5TCU3V9HW25
TPM2	NM_001301227.2 linkuse as main transcript	c.773-4_773-3dupCC	splice_region_variant, intron_variant		NP_001288156.1	A7XZE4V9HW25
TPM2	NM_213674.1 linkuse as main transcript	c.772+1001_772+1002dupCC	intron_variant		NP_998839.1	P07951-2V9HW25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPM2	ENST00000645482.3 linkuse as main transcript	c.773-4_773-3dupCC		splice_region_variant, intron_variant			NM_003289.4	ENSP00000496494.2		P07951-1

Frequencies

GnomAD3 genomes

AF:

0.0788

AC:

11831

AN:

150148

Hom.:

769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.0544

Gnomad ASJ

AF:

0.0306

Gnomad EAS

AF:

0.000977

Gnomad SAS

AF:

0.0136

Gnomad FIN

AF:

0.0298

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0461

Gnomad OTH

AF:

0.0707

GnomAD3 exomes

AF:

0.0322

AC:

4958

AN:

154034

Hom.:

AF XY:

0.0298

AC XY:

2418

AN XY:

81146

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.0256

Gnomad ASJ exome

AF:

0.0298

Gnomad EAS exome

AF:

0.00192

Gnomad SAS exome

AF:

0.0108

Gnomad FIN exome

AF:

0.0213

Gnomad NFE exome

AF:

0.0361

Gnomad OTH exome

AF:

0.0323

GnomAD4 exome

AF:

0.0345

AC:

45675

AN:

1322558

Hom.:

129

Cov.:

AF XY:

0.0339

AC XY:

22169

AN XY:

654466

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.0262

Gnomad4 ASJ exome

AF:

0.0279

Gnomad4 EAS exome

AF:

0.00119

Gnomad4 SAS exome

AF:

0.0122

Gnomad4 FIN exome

AF:

0.0214

Gnomad4 NFE exome

AF:

0.0357

Gnomad4 OTH exome

AF:

0.0356

GnomAD4 genome

AF:

0.0788

AC:

11848

AN:

150266

Hom.:

770

Cov.:

AF XY:

0.0764

AC XY:

5606

AN XY:

73416

show subpopulations

Gnomad4 AFR

AF:

0.179

Gnomad4 AMR

AF:

0.0544

Gnomad4 ASJ

AF:

0.0306

Gnomad4 EAS

AF:

0.000979

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.0298

Gnomad4 NFE

AF:

0.0461

Gnomad4 OTH

AF:

0.0699

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Eurofins Ntd Llc (ga)	Jul 24, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 21, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Arthrogryposis, distal, type 1A;C0546264:Congenital myopathy with fiber type disproportion;C1836447:Congenital myopathy 23

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 28, 2022

- -

Arthrogryposis, distal, type 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over