chr2-182928655-T-G

Variant names:

• chr2-182928655-T-G
• rs9333279
• NM_013436.5:c.3070+128A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013436.5(NCKAP1):​c.3070+128A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 443,560 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: NCKAP1 NM_013436.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000225 AC: 1 AN: 443560 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 230730

African (AFR) AF: 0.00 AC: 0 AN: 10906

American (AMR) AF: 0.00 AC: 0 AN: 13860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12618

East Asian (EAS) AF: 0.0000348 AC: 1 AN: 28726

South Asian (SAS) AF: 0.00 AC: 0 AN: 31856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3352

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 274746

Other (OTH) AF: 0.00 AC: 0 AN: 24562

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-0.089

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

Other links and lift over

dbSNP: rs9333279; hg19: chr2-183793383;