rs12053259

Positions:

• chr2-105812263-G-A
• chr2-105812263-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003581.5(NCK2):​c.-200-4167G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,120 control chromosomes in the GnomAD database, including 7,008 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 0.29 (7008 hom., cov: 32)
• Consequence: NCK2 NM_003581.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCK2	NM_003581.5	c.-200-4167G>A		intron_variant		ENST00000233154.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCK2	ENST00000233154.9	c.-200-4167G>A		intron_variant		5	NM_003581.5	P1
NCK2	ENST00000393348.6	c.-200-4167G>A		intron_variant		3
NCK2	ENST00000451463.6	c.-200-4167G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43454 AN: 152002 Hom.: 7001 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.286 AC: 43490 AN: 152120 Hom.: 7008 Cov.: 32 AF XY: 0.291 AC XY: 21660 AN XY: 74354

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.276

Alfa AF: 0.333 Hom.: 15174

Bravo AF: 0.270

Asia WGS AF: 0.313 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.87

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: rs12053259; hg19: chr2-106428720;