1-58575789-A-G

Position:

• chr1-58575789-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002353.3(TACSTD2):​c.*396T>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 0.00483 in 201,416 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (4 hom.)
• Consequence: TACSTD2 NM_002353.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.654

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 1-58575789-A-G is Benign according to our data. Variant chr1-58575789-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 297755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00476 (725/152344) while in subpopulation AMR AF= 0.0081 (124/15302). AF 95% confidence interval is 0.00717. There are 7 homozygotes in gnomad4. There are 342 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACSTD2	NM_002353.3	c.*396T>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.*396T>C		3_prime_UTR_variant	1/1		NM_002353.3	ENSP00000360269.2

Frequencies

GnomAD3 genomes AF: 0.00476 AC: 725 AN: 152226 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00772

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.00505 AC: 248 AN: 49072 Hom.: 4 Cov.: 0 AF XY: 0.00458 AC XY: 115 AN XY: 25102

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.00564

Gnomad4 ASJ exome AF: 0.00815

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00152

Gnomad4 FIN exome AF: 0.00142

Gnomad4 NFE exome AF: 0.00616

Gnomad4 OTH exome AF: 0.00669

GnomAD4 genome AF: 0.00476 AC: 725 AN: 152344 Hom.: 7 Cov.: 33 AF XY: 0.00459 AC XY: 342 AN XY: 74508

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.00810

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00772

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00662 Hom.: 1

Bravo AF: 0.00485

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Gelatinous droplike corneal dystrophy Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.42

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: rs41313365; hg19: chr1-59041461;