Genetic Variant NCKAP1:c.3070+113T>C (chr2-182928670-A-G) – 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+113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 652,150 control chromosomes in the GnomAD database, including 198,449 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 0.67 ( 37582 hom., cov: 32)

Exomes 𝑓: 0.80 ( 160867 hom. )

Consequence

NCKAP1
NM_013436.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.66

Publications

5 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCKAP1	NM_013436.5	MANE Select	c.3070+113T>C	intron	N/A	NP_038464.1	Q9Y2A7-1
NCKAP1	NM_205842.3		c.3088+113T>C	intron	N/A	NP_995314.1	Q9Y2A7-2
NCKAP1	NM_001437267.1		c.3082+113T>C	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.3070+113T>C	intron	N/A	ENSP00000355348.3	Q9Y2A7-1
NCKAP1	ENST00000360982.2	TSL:1	c.3088+113T>C	intron	N/A	ENSP00000354251.2	Q9Y2A7-2
NCKAP1	ENST00000888539.1		c.3085+113T>C	intron	N/A	ENSP00000558598.1

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

101960

AN:

151520

Hom.:

37572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.859

Gnomad AMR

AF:

0.755

Gnomad ASJ

AF:

0.704

Gnomad EAS

AF:

0.960

Gnomad SAS

AF:

0.871

Gnomad FIN

AF:

0.868

Gnomad MID

AF:

0.678

Gnomad NFE

AF:

0.781

Gnomad OTH

AF:

0.682

GnomAD4 exome

AF:

0.796

AC:

398473

AN:

500514

Hom.:

160867

AF XY:

0.800

AC XY:

208268

AN XY:

260472

show subpopulations

African (AFR)

AF:

0.348

AC:

4089

AN:

11766

American (AMR)

AF:

0.789

AC:

12244

AN:

15522

Ashkenazi Jewish (ASJ)

AF:

0.709

AC:

9456

AN:

13346

East Asian (EAS)

AF:

0.957

AC:

28077

AN:

29352

South Asian (SAS)

AF:

0.868

AC:

31292

AN:

36066

European-Finnish (FIN)

AF:

0.867

AC:

38276

AN:

44126

Middle Eastern (MID)

AF:

0.698

AC:

2476

AN:

3546

European-Non Finnish (NFE)

AF:

0.787

AC:

251958

AN:

320020

Other (OTH)

AF:

0.770

AC:

20605

AN:

26770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

3855

7710

11566

15421

19276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2638

5276

7914

10552

13190

<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:

0.673

AC:

102002

AN:

151636

Hom.:

37582

Cov.:

AF XY:

0.681

AC XY:

50438

AN XY:

74096

show subpopulations

African (AFR)

AF:

0.349

AC:

14449

AN:

41410

American (AMR)

AF:

0.756

AC:

11494

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.704

AC:

2441

AN:

3466

East Asian (EAS)

AF:

0.960

AC:

4956

AN:

5160

South Asian (SAS)

AF:

0.872

AC:

4206

AN:

4824

European-Finnish (FIN)

AF:

0.868

AC:

9149

AN:

10538

Middle Eastern (MID)

AF:

0.668

AC:

195

AN:

292

European-Non Finnish (NFE)

AF:

0.781

AC:

52901

AN:

67730

Other (OTH)

AF:

0.683

AC:

1431

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1402

2805

4207

5610

7012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<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:

0.749

Hom.:

175753

Bravo

AF:

0.649

Asia WGS

AF:

0.850

AC:

2952

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.21

(source)

DANN

Benign

0.54

PhyloP100

-1.7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over