1-58575983-T-C

Position:

• chr1-58575983-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002353.3(TACSTD2):​c.*202A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 668,470 control chromosomes in the GnomAD database, including 8,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1701 hom., cov: 32)
  • Exomes 𝑓: 0.16 (6807 hom.)
• Consequence: TACSTD2 NM_002353.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.819

Genes affected

TACSTD2 (HGNC:11530): (tumor associated calcium signal transducer 2) This intronless gene encodes a carcinoma-associated antigen. This antigen is a cell surface receptor that transduces calcium signals. Mutations of this gene have been associated with gelatinous drop-like corneal dystrophy.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-58575983-T-C is Benign according to our data. Variant chr1-58575983-T-C is described in ClinVar as [Benign]. Clinvar id is 297758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACSTD2	NM_002353.3	c.*202A>G		3_prime_UTR_variant	1/1	ENST00000371225.4	NP_002344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACSTD2	ENST00000371225.4	c.*202A>G		3_prime_UTR_variant	1/1		NM_002353.3	ENSP00000360269	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22298 AN: 152082 Hom.: 1700 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.157 AC: 81095 AN: 516270 Hom.: 6807 Cov.: 6 AF XY: 0.157 AC XY: 41908 AN XY: 267700

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.0553

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.147 AC: 22311 AN: 152200 Hom.: 1701 Cov.: 32 AF XY: 0.141 AC XY: 10488 AN XY: 74436

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0525

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0937

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.139

Alfa AF: 0.159 Hom.: 395

Bravo AF: 0.148

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Gelatinous droplike corneal dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	16
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs41313363; hg19: chr1-59041655; COSMIC: COSV64666966;