rs2275864

chr1-201358967-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 1-201358967-G-A 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TNNT2	NM_001276345.2			downstream_gene_variant		ENST00000656932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNT2	ENST00000656932.1			downstream_gene_variant			NM_001276345.2	A2

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

Gnomad4 AFR exome AF: 0.0154

Gnomad4 AMR exome AF: 0.0281

Gnomad4 ASJ exome AF: 0.0140

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.0194

Gnomad4 FIN exome AF: 0.0284

Gnomad4 NFE exome AF: 0.0147

Gnomad4 OTH exome AF: 0.0246

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

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.0356

Gnomad4 NFE AF: 0.0141

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0180 Hom.: 98

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2275864; hg19: chr1-201328095;