17-41054958-G-A

Position:

• chr17-41054958-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033032.3(KRTAP2-2):​c.254C>T​(p.Thr85Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 12)
  • Exomes 𝑓: 0.0 (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: 2.98

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22077006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP2-2	NM_033032.3	c.254C>T	p.Thr85Met	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	c.254C>T	p.Thr85Met	missense_variant	1/1		NM_033032.3	ENSP00000381494	P1

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1008636 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 500774

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 12

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.254C>T (p.T85M) alteration is located in exon 1 (coding exon 1) of the KRTAP2-2 gene. This alteration results from a C to T substitution at nucleotide position 254, causing the threonine (T) at amino acid position 85 to be replaced by a methionine (M). 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	Benign	0.095
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	0.75	N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.073
Sift	Benign	0.10	T;T
Sift4G	Benign	0.20	T;T
Vest4		0.34
MutPred		0.27		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.20
ClinPred		0.81	D
GERP RS		4.5
Varity_R		0.040
gMVP		0.059

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: rs1300239928; hg19: chr17-39211210;