rs10496694

Positions:

• chr2-132778594-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP5	NM_207363.3	c.5049+2458C>T		intron_variant		ENST00000409261.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP5	ENST00000409261.6	c.5049+2458C>T		intron_variant		5	NM_207363.3	P1
	ENST00000651100.1	n.458-36007G>A		intron_variant, non_coding_transcript_variant
NCKAP5	ENST00000409213.5	c.1093-4700C>T		intron_variant		5
NCKAP5	ENST00000473859.1	n.262+2458C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0160

Gnomad4 AMR AF: 0.0393

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0673

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0864

Gnomad4 OTH AF: 0.0515

Alfa AF: 0.0773 Hom.: 240

Bravo AF: 0.0505

Asia WGS AF: 0.0320 AC: 110 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.73
DANN	Benign	0.68

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: rs10496694; hg19: chr2-133536167;