1-58576258-C-T

Position:

chr1-58576258-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002353.3(TACSTD2):c.899G>A(p.Arg300Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,613,982 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 4 hom. )

Consequence

TACSTD2
NM_002353.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.494

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006807208).

BP6

Variant 1-58576258-C-T is Benign according to our data. Variant chr1-58576258-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 873846.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00165 (252/152312) while in subpopulation AFR AF= 0.00592 (246/41564). AF 95% confidence interval is 0.00531. There are 1 homozygotes in gnomad4. There are 116 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACSTD2	NM_002353.3 linkuse as main transcript	c.899G>A	p.Arg300Gln	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 linkuse as main transcript	c.899G>A	p.Arg300Gln	missense_variant	1/1		NM_002353.3	ENSP00000360269	P1

Frequencies

GnomAD3 genomes

AF:

0.00166

AC:

252

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00594

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000443

AC:

111

AN:

250356

Hom.:

AF XY:

0.000333

AC XY:

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.00640

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000158

AC:

231

AN:

1461670

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00589

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.00165

AC:

252

AN:

152312

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00592

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000294

Hom.:

Bravo

AF:

0.00181

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000593

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2022

The c.899G>A (p.R300Q) alteration is located in exon 1 (coding exon 1) of the TACSTD2 gene. This alteration results from a G to A substitution at nucleotide position 899, causing the arginine (R) at amino acid position 300 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Gelatinous droplike corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.063

Eigen_PC

Benign

-0.016

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.78

M_CAP

Benign

0.027

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.99

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.8

REVEL

Benign

0.20

Sift

Benign

0.077

Sift4G

Uncertain

0.059

Polyphen

0.49

Vest4

0.24

MVP

0.81

MPC

0.53

ClinPred

0.021

GERP RS

2.5

Varity_R

0.12

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over