rs879900

Variant names:

• chr2-105877891-A-G
• rs879900
• NM_003581.5:c.227-3437A>G

Variant summary

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

The NM_003581.5(NCK2):​c.227-3437A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,066 control chromosomes in the GnomAD database, including 7,496 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 (7496 hom., cov: 32)
• Consequence: NCK2 NM_003581.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.818
• Publications: 7 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]

ENSG00000234162 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003581.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCK2	NM_003581.5	MANE Select	c.227-3437A>G		intron	N/A	NP_003572.2
	NCK2	NM_001004720.3		c.227-3437A>G		intron	N/A	NP_001004720.1	A0A0S2Z4M6
	NCK2	NM_001004722.4		c.227-15091A>G		intron	N/A	NP_001004722.1	E7ERP6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCK2	ENST00000233154.9	TSL:5 MANE Select	c.227-3437A>G		intron	N/A	ENSP00000233154.4	O43639
	NCK2	ENST00000393349.2	TSL:1	c.227-3437A>G		intron	N/A	ENSP00000377018.2	O43639
	NCK2	ENST00000958280.1		c.245-3437A>G		intron	N/A	ENSP00000628339.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45410 AN: 151948 Hom.: 7494 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.299 AC: 45428 AN: 152066 Hom.: 7496 Cov.: 32 AF XY: 0.303 AC XY: 22545 AN XY: 74322

African (AFR) AF: 0.157 AC: 6535 AN: 41502

American (AMR) AF: 0.286 AC: 4364 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 938 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1825 AN: 5154

South Asian (SAS) AF: 0.428 AC: 2060 AN: 4810

European-Finnish (FIN) AF: 0.408 AC: 4319 AN: 10584

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24234 AN: 67976

Other (OTH) AF: 0.290 AC: 612 AN: 2112

Alfa AF: 0.346 Hom.: 4966

Bravo AF: 0.284

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.36
PhyloP100		0.82
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: rs879900; hg19: chr2-106494347;