Genetic Variant TNNT2:c.233+67G>A (chr1-201366771-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001276345.2(TNNT2):c.233+67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,613,446 control chromosomes in the GnomAD database, including 800,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 73389 hom., cov: 30)

Exomes 𝑓: 1.0 ( 727264 hom. )

Consequence

TNNT2
NM_001276345.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.53

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:

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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=-0.97).

BP6

Variant 1-201366771-C-T is Benign according to our data. Variant chr1-201366771-C-T is described in ClinVar as [Benign]. Clinvar id is 1233312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201366771-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNT2	NM_001276345.2 link	c.233+67G>A		intron_variant	Intron 8 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.233+67G>A		intron_variant	Intron 8 of 16		NM_001276345.2	ENSP00000499593.1		P45379-1

Frequencies

GnomAD3 genomes

AF:

0.982

AC:

149298

AN:

152098

Hom.:

73332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.939

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.990

Gnomad ASJ

AF:

0.988

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.988

GnomAD4 exome

AF:

0.998

AC:

1457811

AN:

1461230

Hom.:

727264

Cov.:

AF XY:

0.998

AC XY:

725400

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.941

Gnomad4 AMR exome

AF:

0.995

Gnomad4 ASJ exome

AF:

0.990

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.995

GnomAD4 genome

AF:

0.982

AC:

149415

AN:

152216

Hom.:

73389

Cov.:

AF XY:

0.982

AC XY:

73090

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.939

Gnomad4 AMR

AF:

0.990

Gnomad4 ASJ

AF:

0.988

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.988

Alfa

AF:

0.995

Hom.:

66439

Bravo

AF:

0.979

Asia WGS

AF:

0.996

AC:

3464

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.18

DANN

Benign

0.59

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