chr2-105819909-G-T

Variant names:

• chr2-105819909-G-T
• rs12995333
• NM_003581.5:c.-17+3296G>T

Variant summary

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

The NM_003581.5(NCK2):​c.-17+3296G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,786 control chromosomes in the GnomAD database, including 7,902 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 (7902 hom., cov: 31)
• Consequence: NCK2 NM_003581.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.759
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCK2	NM_003581.5	c.-17+3296G>T		intron_variant	Intron 2 of 4	ENST00000233154.9	NP_003572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCK2	ENST00000233154.9	c.-17+3296G>T		intron_variant	Intron 2 of 4	5	NM_003581.5	ENSP00000233154.4
NCK2	ENST00000393348.6	c.-17+3296G>T		intron_variant	Intron 2 of 3	3		ENSP00000377017.2
NCK2	ENST00000451463.6	c.-17+3296G>T		intron_variant	Intron 2 of 3	2		ENSP00000410428.2
NCK2	ENST00000522586.5	c.-14+3296G>T		intron_variant	Intron 1 of 2	5		ENSP00000431109.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45723 AN: 151670 Hom.: 7896 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.301 AC: 45751 AN: 151786 Hom.: 7902 Cov.: 31 AF XY: 0.308 AC XY: 22831 AN XY: 74172

African (AFR) AF: 0.135 AC: 5588 AN: 41372

American (AMR) AF: 0.281 AC: 4285 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3462

East Asian (EAS) AF: 0.342 AC: 1772 AN: 5174

South Asian (SAS) AF: 0.401 AC: 1926 AN: 4800

European-Finnish (FIN) AF: 0.484 AC: 5083 AN: 10498

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25089 AN: 67926

Other (OTH) AF: 0.284 AC: 599 AN: 2106

Alfa AF: 0.334 Hom.: 17339

Bravo AF: 0.281

Asia WGS AF: 0.314 AC: 1093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.7
DANN	Benign	0.78
PhyloP100		0.76
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: rs12995333; hg19: chr2-106436366;