rs80358227

Positions:

• chr1-58576802-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_002353.3(TACSTD2):​c.355T>A​(p.Cys119Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TACSTD2 NM_002353.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.64

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.988
• PP5: Variant 1-58576802-A-T is Pathogenic according to our data. Variant chr1-58576802-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 16187.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACSTD2	NM_002353.3	c.355T>A	p.Cys119Ser	missense_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.355T>A	p.Cys119Ser	missense_variant	1/1		NM_002353.3	ENSP00000360269	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Gelatinous droplike corneal dystrophy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	A
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Pathogenic	0.91
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.96		Gain of sheet (P = 0.0061);
MVP		0.90
MPC		1.5
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.96
gMVP		0.99

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: rs80358227; hg19: chr1-59042474;