17-41054972-G-C

Variant names:

• chr17-41054972-G-C
• rs1375582289
• NM_033032.3:c.240C>G

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81

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]

ACMG classification

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 rank	MANE	Protein	UniProt
KRTAP2-2	NM_033032.3	c.240C>G	p.Cys80Trp	missense_variant	Exon 1 of 1	ENST00000398477.1	NP_149021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP2-2	ENST00000398477.1	c.240C>G	p.Cys80Trp	missense_variant	Exon 1 of 1	6	NM_033032.3	ENSP00000381494.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 32 AN: 110882 Hom.: 0 Cov.: 14 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.: 0 Cov.: 17 AF XY: 0.00229 AC XY: 1140 AN XY: 498214

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: 32 AN: 110966 Hom.: 0 Cov.: 14 AF XY: 0.000232 AC XY: 12 AN XY: 51704

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.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Pathogenic	0.85	D
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	D
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

Other links and lift over

dbSNP: rs1375582289; hg19: chr17-39211224;