Genetic Variant NCKAP1:c.1762-12C>A (chr2-182962290-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013436.5(NCKAP1):c.1762-12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NCKAP1
NM_013436.5 intron

Scores

Splicing: ADA: 0.0002568

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.48

Publications

10 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

new If you want to explore the variant's impact on the transcript NM_013436.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151838

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

233730

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000776

AC:

AN:

1417742

Hom.:

Cov.:

AF XY:

0.00000850

AC XY:

AN XY:

705984

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32582

American (AMR)

AF:

0.00

AC:

AN:

41360

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25228

East Asian (EAS)

AF:

0.00

AC:

AN:

38758

South Asian (SAS)

AF:

0.00

AC:

AN:

82016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.0000102

AC:

AN:

1081222

Other (OTH)

AF:

0.00

AC:

AN:

58728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74138

African (AFR)

AF:

0.00

AC:

AN:

41308

American (AMR)

AF:

0.00

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67932

Other (OTH)

AF:

0.00

AC:

AN:

2086

Alfa

AF:

0.00

Hom.:

21305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.9

(source)

DANN

Benign

0.81

PhyloP100

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00026

dbscSNV1_RF

Benign

0.10

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: -12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over