Variant 9-35689376-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003289.4(TPM2):c.115-105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,545,900 control chromosomes in the GnomAD database, including 153,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15688 hom., cov: 33)

Exomes 𝑓: 0.44 ( 137681 hom. )

Consequence

TPM2
NM_003289.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -1.84

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-35689376-T-C is Benign according to our data. Variant chr9-35689376-T-C is described in ClinVar as [Benign]. Clinvar id is 140484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-35689376-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPM2	NM_003289.4 linkuse as main transcript	c.115-105A>G		intron_variant		ENST00000645482.3	NP_003280.2	P07951-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPM2	ENST00000645482.3 linkuse as main transcript	c.115-105A>G		intron_variant			NM_003289.4	ENSP00000496494.2		P07951-1

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68785

AN:

151966

Hom.:

15675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.491

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.460

GnomAD4 exome

AF:

0.442

AC:

616701

AN:

1393816

Hom.:

137681

Cov.:

AF XY:

0.444

AC XY:

305766

AN XY:

688726

show subpopulations

Gnomad4 AFR exome

AF:

0.472

Gnomad4 AMR exome

AF:

0.360

Gnomad4 ASJ exome

AF:

0.455

Gnomad4 EAS exome

AF:

0.626

Gnomad4 SAS exome

AF:

0.490

Gnomad4 FIN exome

AF:

0.479

Gnomad4 NFE exome

AF:

0.433

Gnomad4 OTH exome

AF:

0.444

GnomAD4 genome

AF:

0.453

AC:

68826

AN:

152084

Hom.:

15688

Cov.:

AF XY:

0.454

AC XY:

33761

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.472

Gnomad4 AMR

AF:

0.393

Gnomad4 ASJ

AF:

0.454

Gnomad4 EAS

AF:

0.626

Gnomad4 SAS

AF:

0.492

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.433

Gnomad4 OTH

AF:

0.463

Alfa

AF:

0.436

Hom.:

14202

Bravo

AF:

0.449

Asia WGS

AF:

0.577

AC:

2008

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -
not provided, no classification provided	literature only	TPM2 homepage - Leiden Muscular Dystrophy pages	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.1

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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