Genetic Variant KRTAP2-2:p.Ile77Thr (chr17-41054982-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033032.3(KRTAP2-2):c.230T>C(p.Ile77Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000030 ( 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: 0.963

Publications

0 publications found

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:

ENSG00000306126 (HGNC:):

ENSG00000306126 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16983727).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033032.3. 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
	KRTAP2-2	NM_033032.3	MANE Select	c.230T>C	p.Ile77Thr	missense	Exon 1 of 1	NP_149021.2	Q9BYT5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTAP2-2	ENST00000398477.1	TSL:6 MANE Select	c.230T>C	p.Ile77Thr	missense	Exon 1 of 1	ENSP00000381494.1	Q9BYT5
ENSG00000306126	ENST00000815517.1		n.220-5317A>G		intron	N/A
ENSG00000306126	ENST00000815518.1		n.160-5317A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

115638

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000299

AC:

AN:

1004524

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

499554

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000824

AC:

AN:

24278

American (AMR)

AF:

0.0000359

AC:

AN:

27838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18892

East Asian (EAS)

AF:

0.0000579

AC:

AN:

34554

South Asian (SAS)

AF:

0.00

AC:

AN:

65592

European-Finnish (FIN)

AF:

0.000331

AC:

AN:

30256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3226

European-Non Finnish (NFE)

AF:

0.0000172

AC:

AN:

754834

Other (OTH)

AF:

0.0000444

AC:

AN:

45054

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.270

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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

115728

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

54116

African (AFR)

AF:

0.00

AC:

AN:

30090

American (AMR)

AF:

0.00

AC:

AN:

11200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2944

East Asian (EAS)

AF:

0.00

AC:

AN:

4676

South Asian (SAS)

AF:

0.00

AC:

AN:

3370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6636

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

54336

Other (OTH)

AF:

0.00

AC:

AN:

1470

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0048

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.62

M_CAP

Benign

0.0077

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.81

PhyloP100

0.96

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.080

REVEL

Benign

0.21

Sift

Benign

0.11

Sift4G

Benign

0.38

Vest4

0.18

MutPred

0.44

Gain of glycosylation at I77 (P = 0.036)

MVP

0.13

ClinPred

0.25

GERP RS

4.9

PromoterAI

0.0024

Neutral

(source)

Varity_R

0.074

gMVP

0.023

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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