1-58575548-C-T

Position:

• chr1-58575548-C-T

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.*637G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,998 control chromosomes in the GnomAD database, including 6,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (6813 hom., cov: 32)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: TACSTD2 NM_002353.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.707

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=-0.85).
• BP6: Variant 1-58575548-C-T is Benign according to our data. Variant chr1-58575548-C-T is described in ClinVar as [Benign]. Clinvar id is 297752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACSTD2	NM_002353.3	c.*637G>A		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.*637G>A		3_prime_UTR_variant	1/1		NM_002353.3	ENSP00000360269	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38618 AN: 151850 Hom.: 6790 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.133 AC: 4 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.188 AC XY: 3 AN XY: 16

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.254 AC: 38675 AN: 151968 Hom.: 6813 Cov.: 32 AF XY: 0.247 AC XY: 18375 AN XY: 74290

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.229

Alfa AF: 0.205 Hom.: 1876

Bravo AF: 0.268

Asia WGS AF: 0.165 AC: 577 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 13, 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	-0.85
CADD	Benign	5.0
DANN	Benign	0.59

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: rs7333; hg19: chr1-59041220;