chr2-132731824-C-G

Variant names:

• chr2-132731824-C-G
• rs765563733
• NM_207363.3:c.5356G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207363.3(NCKAP5):​c.5356G>C​(p.Ala1786Pro) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1786V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCKAP5 NM_207363.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733
• Publications: 2 publications found

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]

ENSG00000286068 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10577974).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207363.3. 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
	NCKAP5	NM_207363.3	MANE Select	c.5356G>C	p.Ala1786Pro	missense	Exon 17 of 20	NP_997246.2	O14513-1
	NCKAP5	NM_207481.4		c.1399G>C	p.Ala467Pro	missense	Exon 15 of 18	NP_997364.3	O14513-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP5	ENST00000409261.6	TSL:5 MANE Select	c.5356G>C	p.Ala1786Pro	missense	Exon 17 of 20	ENSP00000387128.1	O14513-1
	NCKAP5	ENST00000409213.5	TSL:5	c.1399G>C	p.Ala467Pro	missense	Exon 15 of 18	ENSP00000386952.1	O14513-2
	NCKAP5	ENST00000640590.1	TSL:5	c.226G>C	p.Ala76Pro	missense	Exon 1 of 3	ENSP00000490966.1	A0A1W2PNT1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.27
DANN	Benign	0.96
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.73
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.13
Sift	Benign	0.095	T
Sift4G	Benign	0.14	T
Polyphen		0.76	P
Vest4		0.24
MutPred		0.16		Loss of sheet (P = 0.0104)
MVP		0.37
MPC		0.17
ClinPred		0.35	T
GERP RS		-5.3
PromoterAI		-0.086	Neutral
Varity_R		0.11
gMVP		0.20
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs765563733; hg19: chr2-133489397;