Genetic Variant NM_013436.5:c.3070+128A>G (chr2-182928655-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013436.5(NCKAP1):c.3070+128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 594,402 control chromosomes in the GnomAD database, including 152,899 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 0.62 ( 31973 hom., cov: 33)

Exomes 𝑓: 0.73 ( 120926 hom. )

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NCKAP1	NM_013436.5 link	c.3070+128A>G	intron_variant	Intron 28 of 30	ENST00000361354.9	NP_038464.1	Q9Y2A7-1
NCKAP1	NM_205842.3 link	c.3088+128A>G	intron_variant	Intron 29 of 31		NP_995314.1	Q9Y2A7-2
NCKAP1	NM_001437267.1 link	c.3082+128A>G	intron_variant	Intron 29 of 31		NP_001424196.1
NCKAP1	NM_001437266.1 link	c.3064+128A>G	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>G		intron_variant	Intron 28 of 30	1	NM_013436.5	ENSP00000355348.3		Q9Y2A7-1

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93249

AN:

151540

Hom.:

31968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.849

Gnomad AMR

AF:

0.710

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.857

Gnomad SAS

AF:

0.741

Gnomad FIN

AF:

0.816

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.731

Gnomad OTH

AF:

0.627

GnomAD4 exome

AF:

0.733

AC:

324653

AN:

442744

Hom.:

120926

AF XY:

0.734

AC XY:

169144

AN XY:

230314

show subpopulations

African (AFR)

AF:

0.282

AC:

3071

AN:

10890

American (AMR)

AF:

0.748

AC:

10351

AN:

13830

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

8256

AN:

12600

East Asian (EAS)

AF:

0.853

AC:

24490

AN:

28698

South Asian (SAS)

AF:

0.743

AC:

23607

AN:

31770

European-Finnish (FIN)

AF:

0.811

AC:

34796

AN:

42914

Middle Eastern (MID)

AF:

0.568

AC:

1896

AN:

3340

European-Non Finnish (NFE)

AF:

0.733

AC:

200924

AN:

274168

Other (OTH)

AF:

0.704

AC:

17262

AN:

24534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

4136

8271

12407

16542

20678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1632

3264

4896

6528

8160

<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

AF:

0.615

AC:

93274

AN:

151658

Hom.:

31973

Cov.:

AF XY:

0.622

AC XY:

46063

AN XY:

74112

show subpopulations

African (AFR)

AF:

0.286

AC:

11848

AN:

41406

American (AMR)

AF:

0.710

AC:

10812

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.652

AC:

2261

AN:

3468

East Asian (EAS)

AF:

0.857

AC:

4420

AN:

5158

South Asian (SAS)

AF:

0.741

AC:

3578

AN:

4826

European-Finnish (FIN)

AF:

0.816

AC:

8582

AN:

10518

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.731

AC:

49519

AN:

67758

Other (OTH)

AF:

0.628

AC:

1320

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1552

3104

4656

6208

7760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.650

Hom.:

4484

Bravo

AF:

0.594

Asia WGS

AF:

0.726

AC:

2520

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.5

(source)

DANN

Benign

0.44

PhyloP100

-0.089

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over