2-132731979-G-C

Position:

• chr2-132731979-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207363.3(NCKAP5):​c.5201C>G​(p.Ser1734Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,632 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: NCKAP5 NM_207363.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

Genes affected

NCKAP5 (HGNC:29847): (NCK associated protein 5) Predicted to be involved in microtubule bundle formation and microtubule depolymerization. Predicted to be active in microtubule plus-end. [provided by Alliance of Genome Resources, Apr 2022]

NCKAP5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCKAP5	NM_207363.3	c.5201C>G	p.Ser1734Trp	missense_variant	17/20	ENST00000409261.6	NP_997246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCKAP5	ENST00000409261.6	c.5201C>G	p.Ser1734Trp	missense_variant	17/20	5	NM_207363.3	ENSP00000387128.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248698 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134912

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461632 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Nov 11, 2024

The c.5201C>G (p.S1734W) alteration is located in exon 17 (coding exon 15) of the NCKAP5 gene. This alteration results from a C to G substitution at nucleotide position 5201, causing the serine (S) at amino acid position 1734 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	Benign	0.34
BayesDel_addAF	Benign	0.0086	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.;T;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.053
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M;.;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.5	D;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.68
MutPred		0.23		Loss of disorder (P = 7e-04);Loss of disorder (P = 7e-04);.;.;
MVP		0.48
MPC		0.29
ClinPred		0.96	D
GERP RS		3.4
Varity_R		0.27
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs563676043; hg19: chr2-133489552;