Variant rs2275863 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_001276345.2(TNNT2):c.811-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,568,964 control chromosomes in the GnomAD database, including 19,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 5513 hom., cov: 32)

Exomes 𝑓: 0.12 ( 13664 hom. )

Consequence

TNNT2
NM_001276345.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.984

Variant links:

Genes affected

TNNT2 (HGNC:11949): (troponin T2, cardiac type) This gene encodes the cardiac isoform of troponin T. The encoded protein is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with dilated cardiomyopathy. [provided by RefSeq, May 2022]

TNNT2 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=-0.87).

BP6

Variant 1-201359696-G-A is Benign according to our data. Variant chr1-201359696-G-A is described in ClinVar as [Benign]. Clinvar id is 256846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201359696-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNNT2	NM_001276345.2 linkuse as main transcript	c.811-33C>T		intron_variant		ENST00000656932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNT2	ENST00000656932.1 linkuse as main transcript	c.811-33C>T		intron_variant			NM_001276345.2	A2	P45379-1

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32943

AN:

152004

Hom.:

5485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.0982

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.155

AC:

28841

AN:

186038

Hom.:

3211

AF XY:

0.153

AC XY:

15099

AN XY:

98730

show subpopulations

Gnomad AFR exome

AF:

0.486

Gnomad AMR exome

AF:

0.0989

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.271

Gnomad SAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.0989

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.118

AC:

167727

AN:

1416840

Hom.:

13664

Cov.:

AF XY:

0.120

AC XY:

84189

AN XY:

700844

show subpopulations

Gnomad4 AFR exome

AF:

0.492

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.0945

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.217

AC:

33016

AN:

152124

Hom.:

5513

Cov.:

AF XY:

0.218

AC XY:

16247

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.473

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.260

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.0982

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.116

Hom.:

1988

Bravo

AF:

0.228

Asia WGS

AF:

0.263

AC:

914

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Dilated cardiomyopathy 1D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 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. -

Cardiomyopathy, familial restrictive, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Hypertrophic cardiomyopathy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.038

DANN

Benign

0.77

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