Variant 9-35682300-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000378292.9(TPM2):c.773-137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,018,706 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 13 hom., cov: 33)

Exomes 𝑓: 0.013 ( 90 hom. )

Consequence

TPM2
ENST00000378292.9 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.854

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 9-35682300-T-C is Benign according to our data. Variant chr9-35682300-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1193556.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00976 (1484/152108) while in subpopulation NFE AF= 0.015 (1018/67994). AF 95% confidence interval is 0.0142. There are 13 homozygotes in gnomad4. There are 717 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1484 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPM2	NM_001301226.2 linkuse as main transcript	c.773-137A>G		intron_variant
TPM2	NM_213674.1 linkuse as main transcript	c.773-137A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Appris	UniProt
TPM2	ENST00000378292.9 linkuse as main transcript	c.773-137A>G	intron_variant		1		P07951-2
TPM2	ENST00000644325.1 linkuse as main transcript	c.*408A>G	3_prime_UTR_variant	4/4
TPM2	ENST00000329305.6 linkuse as main transcript	c.773-137A>G	intron_variant		2	A1
TPM2	ENST00000643485.1 linkuse as main transcript	n.1549A>G	non_coding_transcript_exon_variant	8/8

Frequencies

GnomAD3 genomes

AF:

0.00976

AC:

1484

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00300

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00459

Gnomad FIN

AF:

0.0161

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.0128

AC:

11078

AN:

866598

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

5646

AN XY:

446450

show subpopulations

Gnomad4 AFR exome

AF:

0.00246

Gnomad4 AMR exome

AF:

0.00449

Gnomad4 ASJ exome

AF:

0.00473

Gnomad4 EAS exome

AF:

0.000120

Gnomad4 SAS exome

AF:

0.00491

Gnomad4 FIN exome

AF:

0.0182

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00976

AC:

1484

AN:

152108

Hom.:

Cov.:

AF XY:

0.00964

AC XY:

717

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00299

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00459

Gnomad4 FIN

AF:

0.0161

Gnomad4 NFE

AF:

0.0150

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00770

Hom.:

Bravo

AF:

0.00824

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.26

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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