2-105767281-G-T

Variant names:

• chr2-105767281-G-T
• rs4851854
• NM_003581.5:c.-201+22143G>T

Variant summary

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

The NM_003581.5(NCK2):​c.-201+22143G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,160 control chromosomes in the GnomAD database, including 9,761 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 0.34 (9761 hom., cov: 33)
• Consequence: NCK2 NM_003581.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295
• Publications: 3 publications found

Genes affected

NCK2 (HGNC:7665): (NCK adaptor protein 2) This gene encodes a member of the NCK family of adaptor proteins. The protein contains three SH3 domains and one SH2 domain. The protein has no known catalytic function but has been shown to bind and recruit various proteins involved in the regulation of receptor protein tyrosine kinases. It is through these regulatory activities that this protein is believed to be involved in cytoskeletal reorganization. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCK2	NM_003581.5	c.-201+22143G>T		intron_variant	Intron 1 of 4	ENST00000233154.9	NP_003572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCK2	ENST00000233154.9	c.-201+22143G>T		intron_variant	Intron 1 of 4	5	NM_003581.5	ENSP00000233154.4
NCK2	ENST00000393348.6	c.-201+21394G>T		intron_variant	Intron 1 of 3	3		ENSP00000377017.2
NCK2	ENST00000451463.6	c.-201+22143G>T		intron_variant	Intron 1 of 3	2		ENSP00000410428.2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51227 AN: 152042 Hom.: 9756 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.337 AC: 51256 AN: 152160 Hom.: 9761 Cov.: 33 AF XY: 0.335 AC XY: 24888 AN XY: 74384

African (AFR) AF: 0.147 AC: 6092 AN: 41506

American (AMR) AF: 0.373 AC: 5705 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2385 AN: 5172

South Asian (SAS) AF: 0.345 AC: 1663 AN: 4824

European-Finnish (FIN) AF: 0.385 AC: 4078 AN: 10580

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28789 AN: 67994

Other (OTH) AF: 0.371 AC: 784 AN: 2116

Alfa AF: 0.361 Hom.: 1868

Bravo AF: 0.331

Asia WGS AF: 0.408 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.55
PhyloP100		-0.29
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: rs4851854; hg19: chr2-106383738; COSMIC: COSV51889641;