dbSNP rs80358228: TACSTD2:p.Leu186Pro (chr1-58576600-A-G) – ACMG Classification: Likely_pathogenic (7 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_002353.3(TACSTD2):c.557T>C(p.Leu186Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,992 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TACSTD2
NM_002353.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.53

Publications

13 publications found

Variant links:

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

TACSTD2 links:

ENSG00000283445 (HGNC:):

ENSG00000283445 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.985

PP5

Variant 1-58576600-A-G is Pathogenic according to our data. Variant chr1-58576600-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 16189.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACSTD2	NM_002353.3 link	c.557T>C	p.Leu186Pro	missense_variant	Exon 1 of 1	ENST00000371225.4	NP_002344.2	P09758

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TACSTD2	ENST00000371225.4 link	c.557T>C	p.Leu186Pro	missense_variant	Exon 1 of 1	6	NM_002353.3	ENSP00000360269.2	P09758
ENSG00000283445	ENST00000637377.2 link	n.161+224A>G		intron_variant	Intron 1 of 8	5
ENSG00000283445	ENST00000767021.1 link	n.188+224A>G		intron_variant	Intron 1 of 4
ENSG00000283445	ENST00000767022.1 link	n.142+224A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459992

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111488

Other (OTH)

AF:

0.00

AC:

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Gelatinous droplike corneal dystrophy

Pathogenic:1

Jan 01, 2005

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.99

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.7

PhyloP100

3.5

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.90

MutPred

0.84

Loss of stability (P = 0.0021);

MVP

0.92

MPC

1.7

ClinPred

0.98

GERP RS

4.1

Varity_R

0.77

gMVP

0.94

Mutation Taster

=17/83

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over