rs879900

Positions:

• chr2-105877891-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCK2	NM_003581.5	c.227-3437A>G		intron_variant		ENST00000233154.9	NP_003572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCK2	ENST00000233154.9	c.227-3437A>G		intron_variant		5	NM_003581.5	ENSP00000233154	P1
	ENST00000652190.1	n.752-3155T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.290

Alfa AF: 0.349 Hom.: 4491

Bravo AF: 0.284

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.36

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: rs879900; hg19: chr2-106494347;