1-58575764-T-C

Variant names:

• chr1-58575764-T-C
• rs9583
• NM_002353.3:c.*421A>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.*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
• 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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.*421A>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.*421A>G		3_prime_UTR	Exon 1 of 1	ENSP00000360269.2	P09758

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

African (AFR) AF: 0.124 AC: 51 AN: 412

American (AMR) AF: 0.0738 AC: 234 AN: 3170

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 63 AN: 620

East Asian (EAS) AF: 0.000642 AC: 1 AN: 1558

South Asian (SAS) AF: 0.0516 AC: 235 AN: 4554

European-Finnish (FIN) AF: 0.0606 AC: 77 AN: 1270

Middle Eastern (MID) AF: 0.0818 AC: 9 AN: 110

European-Non Finnish (NFE) AF: 0.0854 AC: 1772 AN: 20760

Other (OTH) AF: 0.0865 AC: 158 AN: 1826

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

African (AFR) AF: 0.189 AC: 7840 AN: 41490

American (AMR) AF: 0.0945 AC: 1445 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3472

East Asian (EAS) AF: 0.00250 AC: 13 AN: 5190

South Asian (SAS) AF: 0.0597 AC: 288 AN: 4822

European-Finnish (FIN) AF: 0.0782 AC: 829 AN: 10600

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0999 AC: 6791 AN: 68010

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.105 Hom.: 1198

Bravo AF: 0.122

Asia WGS AF: 0.0530 AC: 185 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	-0.78
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		0.48
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: rs9583; hg19: chr1-59041436;