rs2271671

Variant names:

• chr2-182962290-G-A
• rs2271671
• NM_013436.5:c.1762-12C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-182962290-G-A
• chr2-182962290-G-C
• chr2-182962290-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013436.5(NCKAP1):​c.1762-12C>T variant causes a 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 intron
• Scores: Splicing: ADA: 0.00008718
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.48
• Publications: 10 publications found

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]

NCKAP1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1229018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013436.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP1	NM_013436.5	MANE Select	c.1762-12C>T		intron	N/A	NP_038464.1	Q9Y2A7-1
	NCKAP1	NM_205842.3		c.1780-12C>T		intron	N/A	NP_995314.1	Q9Y2A7-2
	NCKAP1	NM_001437267.1		c.1774-12C>T		intron	N/A	NP_001424196.1	A0A994J6K9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP1	ENST00000361354.9	TSL:1 MANE Select	c.1762-12C>T		intron	N/A	ENSP00000355348.3	Q9Y2A7-1
	NCKAP1	ENST00000360982.2	TSL:1	c.1780-12C>T		intron	N/A	ENSP00000354251.2	Q9Y2A7-2
	NCKAP1	ENST00000888539.1		c.1762-12C>T		intron	N/A	ENSP00000558598.1

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

GnomAD2 exomes AF: 0.721 AC: 168599 AN: 233730 AF XY: 0.726

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 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

African (AFR) AF: 0.256 AC: 8327 AN: 32508

American (AMR) AF: 0.765 AC: 31572 AN: 41260

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 16249 AN: 25198

East Asian (EAS) AF: 0.842 AC: 32645 AN: 38754

South Asian (SAS) AF: 0.727 AC: 59536 AN: 81868

European-Finnish (FIN) AF: 0.798 AC: 41632 AN: 52176

Middle Eastern (MID) AF: 0.581 AC: 3272 AN: 5636

European-Non Finnish (NFE) AF: 0.729 AC: 786171 AN: 1078898

Other (OTH) AF: 0.704 AC: 41236 AN: 58594

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

African (AFR) AF: 0.286 AC: 11822 AN: 41400

American (AMR) AF: 0.711 AC: 10826 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2255 AN: 3472

East Asian (EAS) AF: 0.856 AC: 4436 AN: 5184

South Asian (SAS) AF: 0.742 AC: 3572 AN: 4816

European-Finnish (FIN) AF: 0.816 AC: 8615 AN: 10554

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49534 AN: 67918

Other (OTH) AF: 0.629 AC: 1324 AN: 2106

Alfa AF: 0.697 Hom.: 21305

Bravo AF: 0.592

Asia WGS AF: 0.723 AC: 2510 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2271671; hg19: chr2-183827018;