rs2013042966

Variant names:

• chr17-41054844-C-G
• rs2013042966
• NM_033032.3:c.368G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033032.3(KRTAP2-2):​c.368G>C​(p.Cys123Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.2e-7 (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: 0.979
• Publications: 0 publications found

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]

ENSG00000306126 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38207793).

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.368G>C	p.Cys123Ser	missense	Exon 1 of 1	NP_149021.2	Q9BYT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP2-2	ENST00000398477.1	TSL:6 MANE Select	c.368G>C	p.Cys123Ser	missense	Exon 1 of 1	ENSP00000381494.1	Q9BYT5
	ENSG00000306126	ENST00000815517.1		n.220-5455C>G		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-5455C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.24e-7 AC: 1 AN: 1381800 Hom.: 0 Cov.: 33 AF XY: 0.00000147 AC XY: 1 AN XY: 680866

African (AFR) AF: 0.00 AC: 0 AN: 30906

American (AMR) AF: 0.00 AC: 0 AN: 34972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24856

East Asian (EAS) AF: 0.00 AC: 0 AN: 35464

South Asian (SAS) AF: 0.00 AC: 0 AN: 77682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4062

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076278

Other (OTH) AF: 0.0000174 AC: 1 AN: 57428

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.064	T
Eigen	Benign	0.14
Eigen_PC	Benign	-0.012
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.98
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.34
MutPred		0.63		Gain of phosphorylation at C123 (P = 0.0203)
MVP		0.085
ClinPred		0.73	D
GERP RS		3.0
PromoterAI		0.00040	Neutral
Varity_R		0.81
gMVP		0.078

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

Other links and lift over

dbSNP: rs2013042966; hg19: chr17-39211096;