2-133508430-A-G

Position:

• chr2-133508430-A-G

Variant summary

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

The NM_207363.3(NCKAP5):​c.69+9028T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 152,258 control chromosomes in the GnomAD database, including 684 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 0.076 (684 hom., cov: 33)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP5	NM_207363.3	c.69+9028T>C		intron_variant		ENST00000409261.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP5	ENST00000409261.6	c.69+9028T>C		intron_variant		5	NM_207363.3	P1
NCKAP5	ENST00000427594.5	c.56+9028T>C		intron_variant		1
NCKAP5	ENST00000358991.4	c.69+9028T>C		intron_variant		5
NCKAP5	ENST00000409213.5	c.69+9028T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0763 AC: 11608 AN: 152140 Hom.: 681 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.0738

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

GnomAD4 genome AF: 0.0764 AC: 11628 AN: 152258 Hom.: 684 Cov.: 33 AF XY: 0.0776 AC XY: 5777 AN XY: 74452

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0995

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.0441

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0394

Gnomad4 OTH AF: 0.0726

Alfa AF: 0.0685 Hom.: 119

Bravo AF: 0.0852

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.2
DANN	Benign	0.45

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: rs16826005; hg19: chr2-134266001;