chr20-45827420-T-C

Variant names:

• chr20-45827420-T-C
• rs373018
• ENST00000372557.1:c.-42-2586A>G

Variant summary

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

The ENST00000372557.1(TNNC2):​c.-42-2586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 742,138 control chromosomes in the GnomAD database, including 101,652 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 0.46 (16983 hom., cov: 29)
  • Exomes 𝑓: 0.53 (84669 hom.)
• Consequence: TNNC2 ENST00000372557.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• Publications: 6 publications found

Genes affected

TNNC2 (HGNC:11944): (troponin C2, fast skeletal type) Troponin (Tn), a key protein complex in the regulation of striated muscle contraction, is composed of 3 subunits. The Tn-I subunit inhibits actomyosin ATPase, the Tn-T subunit binds tropomyosin and Tn-C, while the Tn-C subunit binds calcium and overcomes the inhibitory action of the troponin complex on actin filaments. The protein encoded by this gene is the Tn-C subunit. [provided by RefSeq, Jul 2008]

TNNC2 Gene-Disease associations (from GenCC):

• congenital myopathy 15

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

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372557.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNC2	NM_003279.3	MANE Select	c.-172A>G		upstream_gene	N/A	NP_003270.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNC2	ENST00000372557.1	TSL:3	c.-42-2586A>G		intron	N/A	ENSP00000361638.1
	TNNC2	ENST00000372555.8	TSL:1 MANE Select	c.-172A>G		upstream_gene	N/A	ENSP00000361636.3

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69016 AN: 150694 Hom.: 16962 Cov.: 29

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.530 AC: 313161 AN: 591328 Hom.: 84669 AF XY: 0.522 AC XY: 159642 AN XY: 305692

African (AFR) AF: 0.268 AC: 4142 AN: 15436

American (AMR) AF: 0.566 AC: 14675 AN: 25936

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 6236 AN: 15700

East Asian (EAS) AF: 0.572 AC: 17998 AN: 31478

South Asian (SAS) AF: 0.383 AC: 20049 AN: 52384

European-Finnish (FIN) AF: 0.583 AC: 21155 AN: 36288

Middle Eastern (MID) AF: 0.454 AC: 1614 AN: 3558

European-Non Finnish (NFE) AF: 0.558 AC: 212021 AN: 379734

Other (OTH) AF: 0.496 AC: 15271 AN: 30814

GnomAD4 genome AF: 0.458 AC: 69058 AN: 150810 Hom.: 16983 Cov.: 29 AF XY: 0.458 AC XY: 33695 AN XY: 73560

African (AFR) AF: 0.270 AC: 11061 AN: 40950

American (AMR) AF: 0.502 AC: 7615 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3464

East Asian (EAS) AF: 0.528 AC: 2660 AN: 5042

South Asian (SAS) AF: 0.380 AC: 1807 AN: 4754

European-Finnish (FIN) AF: 0.580 AC: 6010 AN: 10364

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 36921 AN: 67768

Other (OTH) AF: 0.456 AC: 952 AN: 2086

Alfa AF: 0.454 Hom.: 2724

Bravo AF: 0.449

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		0.27
PromoterAI		0.032	Neutral
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs373018; hg19: chr20-44456059; COSMIC: COSV107472159; COSMIC: COSV107472159;