rs2271671

chr2-182962290-G-Achr2-182962290-G-Cchr2-182962290-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013436.5(NCKAP1):c.1762-12C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,566,778 control chromosomes in the GnomAD database, including 402,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (31965 hom., cov: 31)
  • Exomes 𝑓: 0.72 (370477 hom.)
• Consequence: NCKAP1 NM_013436.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00008718
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.48

Genes affected

NCKAP1 (HGNC:7666): (NCK associated protein 1) Contributes to small GTPase binding activity. Involved in Rac protein signal transduction; positive regulation of Arp2/3 complex-mediated actin nucleation; and positive regulation of lamellipodium assembly. Located in extracellular exosome and focal adhesion. Part of SCAR complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 2-182962290-G-A is Benign according to our data. Variant chr2-182962290-G-A is described in ClinVar as [Benign]. Clinvar id is 1229018.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP1	NM_013436.5	c.1762-12C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000361354.9
NCKAP1	NM_205842.3	c.1780-12C>T		splice_polypyrimidine_tract_variant, intron_variant
NCKAP1	XM_006712200.4	c.1774-12C>T		splice_polypyrimidine_tract_variant, intron_variant
NCKAP1	XM_006712201.4	c.1756-12C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP1	ENST00000361354.9	c.1762-12C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_013436.5	P4

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93292 AN: 151770 Hom.: 31960 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.628

GnomAD3 exomes AF: 0.721 AC: 168599 AN: 233730 Hom.: 62443 AF XY: 0.726 AC XY: 91922 AN XY: 126564

Gnomad AFR exome AF: 0.277

Gnomad AMR exome AF: 0.786

Gnomad ASJ exome AF: 0.654

Gnomad EAS exome AF: 0.854

Gnomad SAS exome AF: 0.738

Gnomad FIN exome AF: 0.810

Gnomad NFE exome AF: 0.729

Gnomad OTH exome AF: 0.722

GnomAD4 exome AF: 0.721 AC: 1020640 AN: 1414892 Hom.: 370477 Cov.: 28 AF XY: 0.721 AC XY: 508348 AN XY: 704616

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.765

Gnomad4 ASJ exome AF: 0.645

Gnomad4 EAS exome AF: 0.842

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.798

Gnomad4 NFE exome AF: 0.729

Gnomad4 OTH exome AF: 0.704

GnomAD4 genome AF: 0.614 AC: 93317 AN: 151886 Hom.: 31965 Cov.: 31 AF XY: 0.621 AC XY: 46111 AN XY: 74218

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.629

Alfa AF: 0.699 Hom.: 19280

Bravo AF: 0.592

Asia WGS AF: 0.723 AC: 2510 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	14
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000087
dbscSNV1_RF	Benign	0.13
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: rs2271671; hg19: chr2-183827018;