2-182928670-A-G

Variant names:

• chr2-182928670-A-G
• rs9333280
• NM_013436.5:c.3070+113T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCKAP1	NM_013436.5	c.3070+113T>C		intron_variant	Intron 28 of 30	ENST00000361354.9	NP_038464.1
NCKAP1	NM_205842.3	c.3088+113T>C		intron_variant	Intron 29 of 31		NP_995314.1
NCKAP1	XM_006712200.4	c.3082+113T>C		intron_variant	Intron 29 of 31		XP_006712263.1
NCKAP1	XM_006712201.4	c.3064+113T>C		intron_variant	Intron 28 of 30		XP_006712264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCKAP1	ENST00000361354.9	c.3070+113T>C		intron_variant	Intron 28 of 30	1	NM_013436.5	ENSP00000355348.3

Frequencies

GnomAD3 genomes AF: 0.673 AC: 101960 AN: 151520 Hom.: 37572 Cov.: 32

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

Gnomad4 AFR exome AF: 0.348

Gnomad4 AMR exome AF: 0.789

Gnomad4 ASJ exome AF: 0.709

Gnomad4 EAS exome AF: 0.957

Gnomad4 SAS exome AF: 0.868

Gnomad4 FIN exome AF: 0.867

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.770

GnomAD4 genome AF: 0.673 AC: 102002 AN: 151636 Hom.: 37582 Cov.: 32 AF XY: 0.681 AC XY: 50438 AN XY: 74096

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.683

Alfa AF: 0.768 Hom.: 90683

Bravo AF: 0.649

Asia WGS AF: 0.850 AC: 2952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs9333280; hg19: chr2-183793398;