rs7510

Variant names:

• chr2-182924921-C-A
• rs7510
• NM_013436.5:c.*781G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-182924921-C-A
• chr2-182924921-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013436.5(NCKAP1):​c.*781G>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.613 in 151,900 control chromosomes in the GnomAD database, including 31,764 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 0.61 (31764 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: NCKAP1 NM_013436.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91
• Publications: 10 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP1	NM_013436.5	MANE Select	c.*781G>T		3_prime_UTR	Exon 31 of 31	NP_038464.1	Q9Y2A7-1
	NCKAP1	NM_205842.3		c.*781G>T		3_prime_UTR	Exon 32 of 32	NP_995314.1	Q9Y2A7-2
	NCKAP1	NM_001437267.1		c.*781G>T		3_prime_UTR	Exon 32 of 32	NP_001424196.1	A0A994J6K9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP1	ENST00000361354.9	TSL:1 MANE Select	c.*781G>T		3_prime_UTR	Exon 31 of 31	ENSP00000355348.3	Q9Y2A7-1
	NCKAP1	ENST00000360982.2	TSL:1	c.*781G>T		3_prime_UTR	Exon 32 of 32	ENSP00000354251.2	Q9Y2A7-2
	NCKAP1	ENST00000888539.1		c.*781G>T		3_prime_UTR	Exon 31 of 31	ENSP00000558598.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93019 AN: 151782 Hom.: 31759 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.627

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.613 AC: 93043 AN: 151900 Hom.: 31764 Cov.: 32 AF XY: 0.618 AC XY: 45901 AN XY: 74214

African (AFR) AF: 0.285 AC: 11802 AN: 41424

American (AMR) AF: 0.711 AC: 10840 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2252 AN: 3464

East Asian (EAS) AF: 0.856 AC: 4440 AN: 5184

South Asian (SAS) AF: 0.739 AC: 3559 AN: 4816

European-Finnish (FIN) AF: 0.797 AC: 8396 AN: 10540

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49494 AN: 67898

Other (OTH) AF: 0.628 AC: 1327 AN: 2112

Alfa AF: 0.662 Hom.: 16899

Bravo AF: 0.592

Asia WGS AF: 0.723 AC: 2508 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		3.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs7510; hg19: chr2-183789649;