rs10496694

Variant names:

• chr2-132778594-G-A
• rs10496694
• NM_207363.3:c.5049+2458C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207363.3(NCKAP5):​c.5049+2458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 152,212 control chromosomes in the GnomAD database, including 360 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.060 (360 hom., cov: 33)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532
• Publications: 0 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP5	NM_207363.3	MANE Select	c.5049+2458C>T		intron	N/A	NP_997246.2
	NCKAP5	NM_207481.4		c.1093-4700C>T		intron	N/A	NP_997364.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP5	ENST00000409261.6	TSL:5 MANE Select	c.5049+2458C>T		intron	N/A	ENSP00000387128.1
	NCKAP5	ENST00000409213.5	TSL:5	c.1093-4700C>T		intron	N/A	ENSP00000386952.1
	NCKAP5	ENST00000473859.1	TSL:3	n.262+2458C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9090 AN: 152094 Hom.: 360 Cov.: 33

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0394

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0676

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0864

Gnomad OTH AF: 0.0521

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0597 AC: 9085 AN: 152212 Hom.: 360 Cov.: 33 AF XY: 0.0597 AC XY: 4446 AN XY: 74418

African (AFR) AF: 0.0160 AC: 666 AN: 41556

American (AMR) AF: 0.0393 AC: 601 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0673 AC: 325 AN: 4830

European-Finnish (FIN) AF: 0.113 AC: 1194 AN: 10588

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0864 AC: 5872 AN: 67970

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0665 Hom.: 340

Bravo AF: 0.0505

Asia WGS AF: 0.0320 AC: 110 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.73
DANN	Benign	0.68
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs10496694; hg19: chr2-133536167;