chr1-58575905-A-G

Position:

• chr1-58575905-A-G

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.*280T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 482,600 control chromosomes in the GnomAD database, including 36,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (17349 hom., cov: 33)
  • Exomes 𝑓: 0.33 (19475 hom.)
• Consequence: TACSTD2 NM_002353.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.573

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=-0.82).
• BP6: Variant 1-58575905-A-G is Benign according to our data. Variant chr1-58575905-A-G is described in ClinVar as [Benign]. Clinvar id is 297756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACSTD2	NM_002353.3	c.*280T>C		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	c.*280T>C		3_prime_UTR_variant	1/1		NM_002353.3	ENSP00000360269.2

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65871 AN: 151986 Hom.: 17312 Cov.: 33

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.328 AC: 108275 AN: 330496 Hom.: 19475 Cov.: 3 AF XY: 0.325 AC XY: 55963 AN XY: 172048

Gnomad4 AFR exome AF: 0.752

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.311

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.434 AC: 65953 AN: 152104 Hom.: 17349 Cov.: 33 AF XY: 0.420 AC XY: 31203 AN XY: 74374

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.401

Alfa AF: 0.362 Hom.: 4400

Bravo AF: 0.452

Asia WGS AF: 0.260 AC: 908 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	-0.82
CADD	Benign	10
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3551; hg19: chr1-59041577; COSMIC: COSV64666960;