rs2275864

Variant names:

• chr1-201358967-G-A
• rs2275864
• NM_001276345.2:c.*243C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-201358967-G-A
• chr1-201358967-G-C
• chr1-201358967-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001276345.2(TNNT2):​c.*243C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 603,476 control chromosomes in the GnomAD database, including 644 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.023 (129 hom., cov: 32)
  • Exomes 𝑓: 0.027 (515 hom.)
• Consequence: TNNT2 NM_001276345.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• dilated cardiomyopathy 1D

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypertrophic cardiomyopathy 3

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• cardiomyopathy, familial restrictive, 3

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial isolated restrictive cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000286600 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNT2	NM_001276345.2	c.*243C>T		downstream_gene_variant		ENST00000656932.1	NP_001263274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNT2	ENST00000656932.1	c.*243C>T		downstream_gene_variant			NM_001276345.2	ENSP00000499593.1

Frequencies

GnomAD3 genomes AF: 0.0232 AC: 3525 AN: 152144 Hom.: 128 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.0271 AC: 12220 AN: 451212 Hom.: 515 Cov.: 4 AF XY: 0.0266 AC XY: 6355 AN XY: 239110

African (AFR) AF: 0.0154 AC: 193 AN: 12530

American (AMR) AF: 0.0281 AC: 605 AN: 21558

Ashkenazi Jewish (ASJ) AF: 0.0140 AC: 194 AN: 13844

East Asian (EAS) AF: 0.160 AC: 4852 AN: 30418

South Asian (SAS) AF: 0.0194 AC: 904 AN: 46506

European-Finnish (FIN) AF: 0.0284 AC: 801 AN: 28242

Middle Eastern (MID) AF: 0.0387 AC: 75 AN: 1936

European-Non Finnish (NFE) AF: 0.0147 AC: 3961 AN: 270362

Other (OTH) AF: 0.0246 AC: 635 AN: 25816

GnomAD4 genome AF: 0.0231 AC: 3524 AN: 152264 Hom.: 129 Cov.: 32 AF XY: 0.0257 AC XY: 1910 AN XY: 74436

African (AFR) AF: 0.0141 AC: 586 AN: 41568

American (AMR) AF: 0.0258 AC: 395 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.191 AC: 986 AN: 5158

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4818

European-Finnish (FIN) AF: 0.0356 AC: 378 AN: 10606

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0141 AC: 962 AN: 68022

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

Alfa AF: 0.0177 Hom.: 215

Bravo AF: 0.0235

Asia WGS AF: 0.107 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.99
DANN	Benign	0.45
PhyloP100		-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2275864; hg19: chr1-201328095;