rs2268943

Variant names:

• chr1-58575384-T-A
• rs2268943
• NM_002353.3:c.*801A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002353.3(TACSTD2):​c.*801A>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,064 control chromosomes in the GnomAD database, including 2,192 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (2192 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TACSTD2 NM_002353.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 4 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACSTD2	NM_002353.3	c.*801A>T		downstream_gene_variant		ENST00000371225.4	NP_002344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACSTD2	ENST00000371225.4	c.*801A>T		downstream_gene_variant		6	NM_002353.3	ENSP00000360269.2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19945 AN: 151946 Hom.: 2188 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0985

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.131 AC: 19965 AN: 152064 Hom.: 2192 Cov.: 32 AF XY: 0.128 AC XY: 9527 AN XY: 74366

African (AFR) AF: 0.296 AC: 12254 AN: 41426

American (AMR) AF: 0.0622 AC: 951 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 296 AN: 3468

East Asian (EAS) AF: 0.124 AC: 645 AN: 5186

South Asian (SAS) AF: 0.102 AC: 493 AN: 4816

European-Finnish (FIN) AF: 0.0466 AC: 493 AN: 10572

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4563 AN: 67996

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.108 Hom.: 176

Bravo AF: 0.140

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.79
PhyloP100		0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2268943; hg19: chr1-59041056;