rs6747023

Variant names:

• chr2-105815399-A-G
• rs6747023
• NM_003581.5:c.-200-1031A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-105815399-A-G
• chr2-105815399-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003581.5(NCK2):​c.-200-1031A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,166 control chromosomes in the GnomAD database, including 7,965 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 0.30 (7965 hom., cov: 33)
• Consequence: NCK2 NM_003581.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCK2	NM_003581.5	c.-200-1031A>G		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.-200-1031A>G		intron_variant	Intron 1 of 4	5	NM_003581.5	ENSP00000233154.4
NCK2	ENST00000393348.6	c.-200-1031A>G		intron_variant	Intron 1 of 3	3		ENSP00000377017.2
NCK2	ENST00000451463.6	c.-200-1031A>G		intron_variant	Intron 1 of 3	2		ENSP00000410428.2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45984 AN: 152048 Hom.: 7958 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.302 AC: 46018 AN: 152166 Hom.: 7965 Cov.: 33 AF XY: 0.309 AC XY: 22953 AN XY: 74378

African (AFR) AF: 0.138 AC: 5727 AN: 41538

American (AMR) AF: 0.284 AC: 4346 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 960 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1772 AN: 5170

South Asian (SAS) AF: 0.402 AC: 1942 AN: 4826

European-Finnish (FIN) AF: 0.481 AC: 5082 AN: 10568

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25126 AN: 68000

Other (OTH) AF: 0.290 AC: 612 AN: 2110

Alfa AF: 0.327 Hom.: 12791

Bravo AF: 0.283

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		0.24
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: rs6747023; hg19: chr2-106431856;