Variant 1-159919671-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000368097.9(TAGLN2):c.345C>A(p.Asp115Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,466 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TAGLN2
ENST00000368097.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

TAGLN2 (HGNC:11554): (transgelin 2) The protein encoded by this gene is similar to the protein transgelin, which is one of the earliest markers of differentiated smooth muscle. The specific function of this protein has not yet been determined, although it is thought to be a tumor suppressor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

TAGLN2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TAGLN2	NM_003564.3 linkuse as main transcript	c.345C>A	p.Asp115Glu	missense_variant	3/5	ENST00000368097.9	NP_003555.1
TAGLN2	NM_001277224.2 linkuse as main transcript	c.408C>A	p.Asp136Glu	missense_variant	3/5		NP_001264153.1
TAGLN2	NM_001277223.2 linkuse as main transcript	c.345C>A	p.Asp115Glu	missense_variant	3/5		NP_001264152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAGLN2	ENST00000368097.9 linkuse as main transcript	c.345C>A	p.Asp115Glu	missense_variant	3/5	1	NM_003564.3	ENSP00000357077	P1	P37802-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251108

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1460466

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.345C>A (p.D115E) alteration is located in exon 3 (coding exon 2) of the TAGLN2 gene. This alteration results from a C to A substitution at nucleotide position 345, causing the aspartic acid (D) at amino acid position 115 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.86

.;D;D;D

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

D;.;D;D

M_CAP

Uncertain

0.093

MetaRNN

Pathogenic

0.95

D;D;D;D

MetaSVM

Uncertain

0.012

MutationAssessor

Pathogenic

3.3

.;M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.9

D;D;D;D

REVEL

Pathogenic

0.71

Sift

Uncertain

0.010

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;.

Polyphen

1.0

.;D;D;.

Vest4

0.91

MutPred

0.91

.;Loss of ubiquitination at K120 (P = 0.0594);Loss of ubiquitination at K120 (P = 0.0594);Loss of ubiquitination at K120 (P = 0.0594);

MVP

0.88

MPC

1.1

ClinPred

0.87

GERP RS

3.1

Varity_R

0.71

gMVP

0.92

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