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GeneBe

2-182935332-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_013436.5(NCKAP1):c.2739T>C(p.Ile913=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00494 in 1,590,640 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0051 ( 30 hom. )

Consequence

NCKAP1
NM_013436.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.07
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-182935332-A-G is Benign according to our data. Variant chr2-182935332-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2651738.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.07 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 490 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NCKAP1NM_013436.5 linkuse as main transcriptc.2739T>C p.Ile913= synonymous_variant 25/31 ENST00000361354.9
NCKAP1NM_205842.3 linkuse as main transcriptc.2757T>C p.Ile919= synonymous_variant 26/32
NCKAP1XM_006712200.4 linkuse as main transcriptc.2751T>C p.Ile917= synonymous_variant 26/32
NCKAP1XM_006712201.4 linkuse as main transcriptc.2733T>C p.Ile911= synonymous_variant 25/31

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NCKAP1ENST00000361354.9 linkuse as main transcriptc.2739T>C p.Ile913= synonymous_variant 25/311 NM_013436.5 P4Q9Y2A7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00322
AC:
490
AN:
152190
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00106
Gnomad AMI
AF:
0.00658
Gnomad AMR
AF:
0.00190
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00393
Gnomad FIN
AF:
0.000565
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00551
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00336
AC:
772
AN:
229850
Hom.:
3
AF XY:
0.00358
AC XY:
447
AN XY:
124994
show subpopulations
Gnomad AFR exome
AF:
0.000873
Gnomad AMR exome
AF:
0.000987
Gnomad ASJ exome
AF:
0.000513
Gnomad EAS exome
AF:
0.000123
Gnomad SAS exome
AF:
0.00519
Gnomad FIN exome
AF:
0.000519
Gnomad NFE exome
AF:
0.00518
Gnomad OTH exome
AF:
0.00347
GnomAD4 exome
AF:
0.00512
AC:
7367
AN:
1438332
Hom.:
30
Cov.:
28
AF XY:
0.00516
AC XY:
3692
AN XY:
715208
show subpopulations
Gnomad4 AFR exome
AF:
0.000782
Gnomad4 AMR exome
AF:
0.00112
Gnomad4 ASJ exome
AF:
0.000698
Gnomad4 EAS exome
AF:
0.000105
Gnomad4 SAS exome
AF:
0.00577
Gnomad4 FIN exome
AF:
0.000585
Gnomad4 NFE exome
AF:
0.00585
Gnomad4 OTH exome
AF:
0.00492
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00322
AC:
490
AN:
152308
Hom.:
2
Cov.:
32
AF XY:
0.00309
AC XY:
230
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00106
Gnomad4 AMR
AF:
0.00189
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00394
Gnomad4 FIN
AF:
0.000565
Gnomad4 NFE
AF:
0.00551
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00430
Hom.:
1
Bravo
AF:
0.00308
Asia WGS
AF:
0.00289
AC:
10
AN:
3472

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2024NCKAP1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
12
Dann
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144374101; hg19: chr2-183800060; API