rs45533739

Variant names:

• chr1-201372047-CAGAAG-C
• rs45533739
• NM_001276345.2:c.53-11_53-7delCTTCT

Your query was ambiguous. Multiple possible variants found:

• chr1-201372047-CAGAAG-C
• chr1-201372047-CAGAAG-CAGAAGAGAAG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:23
• Conservation: PhyloP100: 0.855
• Publications: 10 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypertrophic cardiomyopathy 2

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

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

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

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• 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 -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 Benign/Likely_benign. ClinVar VariationId is 43652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276345.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNT2	NM_001276345.2	MANE Select	c.53-11_53-7delCTTCT		splice_region intron	N/A	NP_001263274.1	P45379-1
	TNNT2	NM_000364.4		c.53-11_53-7delCTTCT		splice_region intron	N/A	NP_000355.2
	TNNT2	NM_001406723.1		c.53-11_53-7delCTTCT		splice_region intron	N/A	NP_001393652.1	P45379-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNT2	ENST00000656932.1	MANE Select	c.53-11_53-7delCTTCT		splice_region intron	N/A	ENSP00000499593.1	P45379-1
	TNNT2	ENST00000367322.6	TSL:1	c.53-11_53-7delCTTCT		splice_region intron	N/A	ENSP00000356291.2	A0A499FJM7
	TNNT2	ENST00000367320.6	TSL:1	c.53-11_53-7delCTTCT		splice_region intron	N/A	ENSP00000356289.2	P45379-12

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81149 AN: 151210 Hom.: 23259 Cov.: 0

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

GnomAD2 exomes AF: 0.602 AC: 151141 AN: 251208 AF XY: 0.606

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 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

African (AFR) AF: 0.294 AC: 9856 AN: 33472

American (AMR) AF: 0.689 AC: 30803 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 17070 AN: 26136

East Asian (EAS) AF: 0.508 AC: 20147 AN: 39696

South Asian (SAS) AF: 0.624 AC: 53822 AN: 86246

European-Finnish (FIN) AF: 0.664 AC: 35464 AN: 53400

Middle Eastern (MID) AF: 0.588 AC: 3388 AN: 5766

European-Non Finnish (NFE) AF: 0.615 AC: 683917 AN: 1111692

Other (OTH) AF: 0.602 AC: 36323 AN: 60376

GnomAD4 genome AF: 0.537 AC: 81189 AN: 151328 Hom.: 23274 Cov.: 0 AF XY: 0.541 AC XY: 39990 AN XY: 73888

African (AFR) AF: 0.310 AC: 12811 AN: 41354

American (AMR) AF: 0.647 AC: 9835 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2266 AN: 3454

East Asian (EAS) AF: 0.487 AC: 2497 AN: 5126

South Asian (SAS) AF: 0.619 AC: 2971 AN: 4800

European-Finnish (FIN) AF: 0.687 AC: 7170 AN: 10436

Middle Eastern (MID) AF: 0.504 AC: 143 AN: 284

European-Non Finnish (NFE) AF: 0.619 AC: 41883 AN: 67676

Other (OTH) AF: 0.554 AC: 1164 AN: 2102

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	9	not specified (9)
-	-	3	Cardiomyopathy (3)
-	-	3	Hypertrophic cardiomyopathy 2 (3)
-	-	1	Cardiomyopathy, familial restrictive, 3 (1)
-	-	1	Dilated cardiomyopathy 1D (1)
-	-	1	Dilated cardiomyopathy 1D;C1861864:Hypertrophic cardiomyopathy 2;C2676271:Cardiomyopathy, familial restrictive, 3 (1)
-	-	1	Dilated Cardiomyopathy, Dominant (1)
-	-	1	Familial restrictive cardiomyopathy (1)
-	-	1	Hypertrophic cardiomyopathy (1)
-	-	1	Left ventricular noncompaction cardiomyopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs45533739; hg19: chr1-201341175;