Variant 9-35682882-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_213674.1(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
NM_213674.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.105

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 107 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TPM2	NM_001301226.2 link	c.773-719G>A	intron_variant		NP_001288155.1	Q5TCU3V9HW25
TPM2	NM_213674.1 link	c.773-719G>A	intron_variant		NP_998839.1	P07951-2V9HW25
TPM2	NM_003289.4 link	c.*277G>A	downstream_gene_variant	ENST00000645482.3	NP_003280.2	P07951-1
TPM2	NM_001301227.2 link	c.*277G>A	downstream_gene_variant		NP_001288156.1	A7XZE4V9HW25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPM2	ENST00000645482.3 link	c.*277G>A		downstream_gene_variant			NM_003289.4	ENSP00000496494.2		P07951-1

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152114

Hom.:

Cov.:

show subpopulations

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:

AN:

135044

Hom.:

AF XY:

0.000729

AC XY:

AN XY:

71344

show subpopulations

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.:

Cov.:

AF XY:

0.000702

AC XY:

452

AN XY:

644016

show subpopulations

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.:

Cov.:

AF XY:

0.000619

AC XY:

AN XY:

74292

show subpopulations

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.:

Bravo

AF:

0.000612

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

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