Genetic Variant NCKAP1:c.3070+128A>T (chr2-182928655-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013436.5(NCKAP1):c.3070+128A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NCKAP1
NM_013436.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0890

Publications

1 publications found

Variant links:

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

NCKAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NCKAP1	NM_013436.5 link	c.3070+128A>T	intron_variant	Intron 28 of 30	ENST00000361354.9	NP_038464.1	Q9Y2A7-1
NCKAP1	NM_205842.3 link	c.3088+128A>T	intron_variant	Intron 29 of 31		NP_995314.1	Q9Y2A7-2
NCKAP1	NM_001437267.1 link	c.3082+128A>T	intron_variant	Intron 29 of 31		NP_001424196.1
NCKAP1	NM_001437266.1 link	c.3064+128A>T	intron_variant	Intron 28 of 30		NP_001424195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCKAP1	ENST00000361354.9 link	c.3070+128A>T		intron_variant	Intron 28 of 30	1	NM_013436.5	ENSP00000355348.3		Q9Y2A7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

443558

Hom.:

AF XY:

0.00

AC XY:

AN XY:

230728

African (AFR)

AF:

0.00

AC:

AN:

10906

American (AMR)

AF:

0.00

AC:

AN:

13860

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12618

East Asian (EAS)

AF:

0.00

AC:

AN:

28724

South Asian (SAS)

AF:

0.00

AC:

AN:

31856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3352

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

274746

Other (OTH)

AF:

0.00

AC:

AN:

24562

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.0

(source)

DANN

Benign

0.55

PhyloP100

-0.089

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over