2-235913925-C-G

Variant names:

• chr2-235913925-C-G
• rs1962550
• NM_001037131.3:c.1324+5019C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037131.3(AGAP1):​c.1324+5019C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,962 control chromosomes in the GnomAD database, including 10,731 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 0.36 (10731 hom., cov: 32)
• Consequence: AGAP1 NM_001037131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 3 publications found

Genes affected

AGAP1 (HGNC:16922): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 1) This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP1	NM_001037131.3	c.1324+5019C>G		intron_variant	Intron 11 of 17	ENST00000304032.13	NP_001032208.1
AGAP1	NM_001436125.1	c.2119+5019C>G		intron_variant	Intron 11 of 17		NP_001423054.1
AGAP1	NM_001436126.1	c.2119+5019C>G		intron_variant	Intron 11 of 16		NP_001423055.1
AGAP1	NM_014914.5	c.1324+5019C>G		intron_variant	Intron 11 of 16		NP_055729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP1	ENST00000304032.13	c.1324+5019C>G		intron_variant	Intron 11 of 17	5	NM_001037131.3	ENSP00000307634.7

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55130 AN: 151846 Hom.: 10727 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.363 AC: 55143 AN: 151962 Hom.: 10731 Cov.: 32 AF XY: 0.362 AC XY: 26895 AN XY: 74284

African (AFR) AF: 0.240 AC: 9927 AN: 41448

American (AMR) AF: 0.331 AC: 5059 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1456 AN: 3468

East Asian (EAS) AF: 0.563 AC: 2915 AN: 5180

South Asian (SAS) AF: 0.637 AC: 3068 AN: 4818

European-Finnish (FIN) AF: 0.354 AC: 3726 AN: 10522

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27727 AN: 67950

Other (OTH) AF: 0.376 AC: 790 AN: 2102

Alfa AF: 0.235 Hom.: 552

Bravo AF: 0.353

Asia WGS AF: 0.567 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.97
DANN	Benign	0.65
PhyloP100		-0.27
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: rs1962550; hg19: chr2-236822569;