dbSNP rs398053705: TNNT2:c.53-11_53-7delCTTCT (chr1-201372047-CAGAAG-C) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_001276345.2(TNNT2):c.53-11_53-7delCTTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,612,828 control chromosomes in the GnomAD database, including 297,642 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23274 hom., cov: 0)

Exomes 𝑓: 0.61 ( 274368 hom. )

Consequence

TNNT2
NM_001276345.2 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:22

Conservation

PhyloP100: 0.855

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:

ENSG00000286600 (HGNC:):

ENSG00000286600 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-201372047-CAGAAG-C is Benign according to our data. Variant chr1-201372047-CAGAAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 43652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201372047-CAGAAG-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNT2	NM_001276345.2 link	c.53-11_53-7delCTTCT		splice_region_variant, intron_variant	Intron 3 of 16	ENST00000656932.1	NP_001263274.1	P45379-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNT2	ENST00000656932.1 link	c.53-11_53-7delCTTCT		splice_region_variant, intron_variant	Intron 3 of 16		NM_001276345.2	ENSP00000499593.1		P45379-1

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81149

AN:

151210

Hom.:

23259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.647

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.687

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.602

AC:

151141

AN:

251208

Hom.:

46677

AF XY:

0.606

AC XY:

82320

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.298

Gnomad AMR exome

AF:

0.693

Gnomad ASJ exome

AF:

0.645

Gnomad EAS exome

AF:

0.480

Gnomad SAS exome

AF:

0.626

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.613

Gnomad OTH exome

AF:

0.621

GnomAD4 exome

AF:

0.610

AC:

890790

AN:

1461500

Hom.:

274368

AF XY:

0.611

AC XY:

444518

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.689

Gnomad4 ASJ exome

AF:

0.653

Gnomad4 EAS exome

AF:

0.508

Gnomad4 SAS exome

AF:

0.624

Gnomad4 FIN exome

AF:

0.664

Gnomad4 NFE exome

AF:

0.615

Gnomad4 OTH exome

AF:

0.602

GnomAD4 genome

AF:

0.537

AC:

81189

AN:

151328

Hom.:

23274

Cov.:

AF XY:

0.541

AC XY:

39990

AN XY:

73888

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.647

Gnomad4 ASJ

AF:

0.656

Gnomad4 EAS

AF:

0.487

Gnomad4 SAS

AF:

0.619

Gnomad4 FIN

AF:

0.687

Gnomad4 NFE

AF:

0.619

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.585

Hom.:

4882

Bravo

AF:

0.523

Asia WGS

AF:

0.527

AC:

1833

AN:

3478

EpiCase

AF:

0.622

EpiControl

AF:

0.616

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:22

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 07, 2006

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 12, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 25, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cardiomyopathy

Benign:3

Mar 09, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 10, 2022

Cohesion Phenomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 03, 2019

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy 2

Benign:3

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Institute of Human Genetics, University of Wuerzburg

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1D

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated Cardiomyopathy, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Nov 21, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiomyopathy, familial restrictive, 3

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Left ventricular noncompaction cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial restrictive cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1D;C1861864:Hypertrophic cardiomyopathy 2;C2676271:Cardiomyopathy, familial restrictive, 3

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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