NM_002353.3:c.*202A>G

Variant names:

• chr1-58575983-T-C
• rs41313363
• NM_002353.3:c.*202A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

TACSTD2 Gene-Disease associations (from GenCC):

• gelatinous drop-like corneal dystrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000283445 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACSTD2	NM_002353.3	MANE Select	c.*202A>G		3_prime_UTR	Exon 1 of 1	NP_002344.2	P09758

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACSTD2	ENST00000371225.4	TSL:6 MANE Select	c.*202A>G		3_prime_UTR	Exon 1 of 1	ENSP00000360269.2	P09758
	ENSG00000283445	ENST00000637377.2	TSL:5	n.-233T>C		upstream_gene	N/A
	ENSG00000283445	ENST00000767021.1		n.-206T>C		upstream_gene	N/A

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

African (AFR) AF: 0.138 AC: 1882 AN: 13648

American (AMR) AF: 0.111 AC: 1867 AN: 16890

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 2269 AN: 13948

East Asian (EAS) AF: 0.0553 AC: 1700 AN: 30728

South Asian (SAS) AF: 0.154 AC: 6713 AN: 43482

European-Finnish (FIN) AF: 0.103 AC: 3081 AN: 29910

Middle Eastern (MID) AF: 0.166 AC: 349 AN: 2104

European-Non Finnish (NFE) AF: 0.175 AC: 59175 AN: 337546

Other (OTH) AF: 0.145 AC: 4059 AN: 28014

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

African (AFR) AF: 0.135 AC: 5586 AN: 41522

American (AMR) AF: 0.122 AC: 1869 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3470

East Asian (EAS) AF: 0.0525 AC: 272 AN: 5180

South Asian (SAS) AF: 0.139 AC: 672 AN: 4826

European-Finnish (FIN) AF: 0.0937 AC: 994 AN: 10606

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11712 AN: 68000

Other (OTH) AF: 0.139 AC: 294 AN: 2112

Alfa AF: 0.159 Hom.: 395

Bravo AF: 0.148

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Gelatinous droplike corneal dystrophy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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