rs2377339

Positions:

• chr2-105840835-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.-16-14213A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 152,268 control chromosomes in the GnomAD database, including 250 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 0.048 (250 hom., cov: 33)
• Consequence: NCK2 NM_003581.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCK2	NM_003581.5	c.-16-14213A>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.-16-14213A>G		intron_variant		5	NM_003581.5	ENSP00000233154	P1
NCK2	ENST00000393348.6	c.-16-14213A>G		intron_variant		3		ENSP00000377017
NCK2	ENST00000451463.6	c.-16-14213A>G		intron_variant		2		ENSP00000410428
NCK2	ENST00000522586.5	c.-13-14216A>G		intron_variant		5		ENSP00000431109

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7248 AN: 152150 Hom.: 251 Cov.: 33

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0698

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0476 AC: 7250 AN: 152268 Hom.: 250 Cov.: 33 AF XY: 0.0446 AC XY: 3319 AN XY: 74460

Gnomad4 AFR AF: 0.0155

Gnomad4 AMR AF: 0.0716

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0410

Gnomad4 FIN AF: 0.0244

Gnomad4 NFE AF: 0.0698

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0635 Hom.: 202

Bravo AF: 0.0522

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.56

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: rs2377339; hg19: chr2-106457291;