Variant 17-41054972-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_033032.3(KRTAP2-2):c.240C>G(p.Cys80Trp) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 14)

Exomes 𝑓: 0.0022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP2-2
NM_033032.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

Variant links:

Genes affected

KRTAP2-2 (HGNC:18905): (keratin associated protein 2-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP2-2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34756345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP2-2	NM_033032.3 linkuse as main transcript	c.240C>G	p.Cys80Trp	missense_variant	1/1	ENST00000398477.1	NP_149021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP2-2	ENST00000398477.1 linkuse as main transcript	c.240C>G	p.Cys80Trp	missense_variant	1/1		NM_033032.3	ENSP00000381494	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

110882

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000703

Gnomad AMI

AF:

0.00140

Gnomad AMR

AF:

0.000282

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000217

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00110

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000325

Gnomad OTH

AF:

0.000713

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00217

AC:

2173

AN:

1003458

Hom.:

Cov.:

AF XY:

0.00229

AC XY:

1140

AN XY:

498214

show subpopulations

Gnomad4 AFR exome

AF:

0.000685

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00443

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.00187

Gnomad4 FIN exome

AF:

0.00803

Gnomad4 NFE exome

AF:

0.00197

Gnomad4 OTH exome

AF:

0.00285

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000288

AC:

AN:

110966

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

51704

show subpopulations

Gnomad4 AFR

AF:

0.0000700

Gnomad4 AMR

AF:

0.000281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000217

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00110

Gnomad4 NFE

AF:

0.000325

Gnomad4 OTH

AF:

0.000705

Alfa

AF:

0.000122

Hom.:

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

Jun 26, 2023

The c.240C>G (p.C80W) alteration is located in exon 1 (coding exon 1) of the KRTAP2-2 gene. This alteration results from a C to G substitution at nucleotide position 240, causing the cysteine (C) at amino acid position 80 to be replaced by a tryptophan (W). 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

0.86

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

T;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.35

T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.022

D;D

Sift4G

Uncertain

0.0060

D;D

Vest4

0.34

MutPred

0.56

Gain of glycosylation at T78 (P = 0.0612);Gain of glycosylation at T78 (P = 0.0612);

MVP

0.46

ClinPred

0.99

GERP RS

5.0

Varity_R

0.45

gMVP

0.050

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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