2-133356915-G-A

Position:

• chr2-133356915-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.70-53805C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,016 control chromosomes in the GnomAD database, including 2,288 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 0.17 (2288 hom., cov: 32)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP5	NM_207363.3	c.70-53805C>T		intron_variant		ENST00000409261.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP5	ENST00000409261.6	c.70-53805C>T		intron_variant		5	NM_207363.3	P1
NCKAP5	ENST00000427594.5	c.57-53805C>T		intron_variant		1
NCKAP5	ENST00000358991.4	c.70-53805C>T		intron_variant		5
NCKAP5	ENST00000409213.5	c.70-53805C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25818 AN: 151898 Hom.: 2289 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.170 AC: 25828 AN: 152016 Hom.: 2288 Cov.: 32 AF XY: 0.170 AC XY: 12642 AN XY: 74282

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.174

Alfa AF: 0.187 Hom.: 567

Bravo AF: 0.169

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.037
DANN	Benign	0.39

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: rs13411233; hg19: chr2-134114487;