chr2-182952858-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_013436.5(NCKAP1):c.2438C>G(p.Ala813Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,082 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Consequence
NCKAP1
NM_013436.5 missense
NM_013436.5 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 8.09
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, NCKAP1
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCKAP1 | NM_013436.5 | c.2438C>G | p.Ala813Gly | missense_variant | 22/31 | ENST00000361354.9 | |
NCKAP1 | NM_205842.3 | c.2456C>G | p.Ala819Gly | missense_variant | 23/32 | ||
NCKAP1 | XM_006712200.4 | c.2450C>G | p.Ala817Gly | missense_variant | 23/32 | ||
NCKAP1 | XM_006712201.4 | c.2432C>G | p.Ala811Gly | missense_variant | 22/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCKAP1 | ENST00000361354.9 | c.2438C>G | p.Ala813Gly | missense_variant | 22/31 | 1 | NM_013436.5 | P4 | |
NCKAP1 | ENST00000360982.2 | c.2456C>G | p.Ala819Gly | missense_variant | 23/32 | 1 | |||
NCKAP1 | ENST00000703824.1 | c.2450C>G | p.Ala817Gly | missense_variant | 23/32 | ||||
NCKAP1 | ENST00000703825.1 | c.2432C>G | p.Ala811Gly | missense_variant | 22/31 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 33
GnomAD3 genomes
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33
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GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74294
GnomAD4 genome
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 24, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of stability (P = 0.0428);.;
MVP
MPC
2.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at