1-58575764-T-C

Position:

• chr1-58575764-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.*421A>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 0.111 in 186,476 control chromosomes in the GnomAD database, including 1,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1269 hom., cov: 33)
  • Exomes 𝑓: 0.076 (156 hom.)
• Consequence: TACSTD2 NM_002353.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.482

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=-0.78).
• BP6: Variant 1-58575764-T-C is Benign according to our data. Variant chr1-58575764-T-C is described in ClinVar as [Benign]. Clinvar id is 297754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACSTD2	NM_002353.3	c.*421A>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.*421A>G		3_prime_UTR_variant	1/1		NM_002353.3	ENSP00000360269	P1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 18004 AN: 152078 Hom.: 1259 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0947

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0782

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.0758 AC: 2600 AN: 34280 Hom.: 156 Cov.: 0 AF XY: 0.0774 AC XY: 1359 AN XY: 17566

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.0738

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.000642

Gnomad4 SAS exome AF: 0.0516

Gnomad4 FIN exome AF: 0.0606

Gnomad4 NFE exome AF: 0.0854

Gnomad4 OTH exome AF: 0.0865

GnomAD4 genome AF: 0.119 AC: 18041 AN: 152196 Hom.: 1269 Cov.: 33 AF XY: 0.115 AC XY: 8523 AN XY: 74406

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.0945

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.00250

Gnomad4 SAS AF: 0.0597

Gnomad4 FIN AF: 0.0782

Gnomad4 NFE AF: 0.0999

Gnomad4 OTH AF: 0.127

Alfa AF: 0.100 Hom.: 834

Bravo AF: 0.122

Asia WGS AF: 0.0530 AC: 185 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	-0.78
CADD	Benign	11
DANN	Benign	0.71

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: rs9583; hg19: chr1-59041436;