2-133472646-G-T

Position:

• chr2-133472646-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207363.3(NCKAP5):​c.69+44812C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,926 control chromosomes in the GnomAD database, including 4,029 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 0.19 (4029 hom., cov: 31)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCKAP5	NM_207363.3	c.69+44812C>A		intron_variant		ENST00000409261.6	NP_997246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCKAP5	ENST00000409261.6	c.69+44812C>A		intron_variant		5	NM_207363.3	ENSP00000387128.1
NCKAP5	ENST00000427594.5	c.54+44812C>A		intron_variant		1		ENSP00000399070.1
NCKAP5	ENST00000409213.5	c.69+44812C>A		intron_variant		5		ENSP00000386952.1
NCKAP5	ENST00000358991.4	c.69+44812C>A		intron_variant		5		ENSP00000351882.4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28776 AN: 151808 Hom.: 4030 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.190 AC: 28796 AN: 151926 Hom.: 4029 Cov.: 31 AF XY: 0.186 AC XY: 13811 AN XY: 74224

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0897

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.0530

Gnomad4 FIN AF: 0.0917

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.158

Alfa AF: 0.112 Hom.: 1343

Bravo AF: 0.204

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.94
DANN	Benign	0.40

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: rs1821625; hg19: chr2-134230217;