chr2-133246182-C-T

Variant names:

• chr2-133246182-C-T
• rs17800749
• NM_207363.3:c.144-32403G>A

Variant summary

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

The NM_207363.3(NCKAP5):​c.144-32403G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,190 control chromosomes in the GnomAD database, including 1,006 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 0.11 (1006 hom., cov: 31)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCKAP5	NM_207363.3	c.144-32403G>A		intron_variant	Intron 4 of 19	ENST00000409261.6	NP_997246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCKAP5	ENST00000409261.6	c.144-32403G>A		intron_variant	Intron 4 of 19	5	NM_207363.3	ENSP00000387128.1
NCKAP5	ENST00000427594.5	c.129-32403G>A		intron_variant	Intron 2 of 4	1		ENSP00000399070.1
NCKAP5	ENST00000409213.5	c.144-32403G>A		intron_variant	Intron 4 of 17	5		ENSP00000386952.1
NCKAP5	ENST00000358991.4	c.144-32403G>A		intron_variant	Intron 3 of 3	5		ENSP00000351882.4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16832 AN: 151074 Hom.: 1007 Cov.: 31

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.111 AC: 16847 AN: 151190 Hom.: 1006 Cov.: 31 AF XY: 0.111 AC XY: 8218 AN XY: 73782

African (AFR) AF: 0.0680 AC: 2795 AN: 41118

American (AMR) AF: 0.133 AC: 2025 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3462

East Asian (EAS) AF: 0.166 AC: 853 AN: 5124

South Asian (SAS) AF: 0.153 AC: 733 AN: 4792

European-Finnish (FIN) AF: 0.0920 AC: 950 AN: 10326

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8746 AN: 67846

Other (OTH) AF: 0.124 AC: 259 AN: 2096

Alfa AF: 0.0720 Hom.: 106

Bravo AF: 0.114

Asia WGS AF: 0.172 AC: 598 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	1.8
DANN	Benign	0.50
PhyloP100		-0.60
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: rs17800749; hg19: chr2-134003754;