Genetic Variant TACSTD2:c.*637G>A (chr1-58575548-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002353.3(TACSTD2):c.*637G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,998 control chromosomes in the GnomAD database, including 6,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6813 hom., cov: 32)

Exomes 𝑓: 0.13 ( 1 hom. )

Consequence

TACSTD2
NM_002353.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.707

Publications

9 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: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

TACSTD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-58575548-C-T is Benign according to our data. Variant chr1-58575548-C-T is described in ClinVar as Benign. ClinVar VariationId is 297752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 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.*637G>A		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.*637G>A		3_prime_UTR	Exon 1 of 1	ENSP00000360269.2	P09758

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38618

AN:

151850

Hom.:

6790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.232

GnomAD4 exome

AF:

0.133

AC:

AN:

Hom.:

Cov.:

AF XY:

0.188

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.154

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.254

AC:

38675

AN:

151968

Hom.:

6813

Cov.:

AF XY:

0.247

AC XY:

18375

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.501

AC:

20733

AN:

41356

American (AMR)

AF:

0.158

AC:

2408

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

670

AN:

3472

East Asian (EAS)

AF:

0.127

AC:

656

AN:

5180

South Asian (SAS)

AF:

0.163

AC:

784

AN:

4820

European-Finnish (FIN)

AF:

0.125

AC:

1318

AN:

10554

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11363

AN:

67996

Other (OTH)

AF:

0.229

AC:

484

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1262

2524

3787

5049

6311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.209

Hom.:

2431

Bravo

AF:

0.268

Asia WGS

AF:

0.165

AC:

577

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Gelatinous droplike corneal dystrophy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.0

(source)

DANN

Benign

0.59

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over