2-235913004-C-T

Position:

• chr2-235913004-C-T

Variant summary

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

The NM_001037131.3(AGAP1):​c.1324+4098C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,154 control chromosomes in the GnomAD database, including 53,684 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 0.84 (53684 hom., cov: 32)
• Consequence: AGAP1 NM_001037131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGAP1	NM_001037131.3	c.1324+4098C>T		intron_variant		ENST00000304032.13	NP_001032208.1
AGAP1	NM_014914.5	c.1324+4098C>T		intron_variant			NP_055729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP1	ENST00000304032.13	c.1324+4098C>T		intron_variant		5	NM_001037131.3	ENSP00000307634

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127268 AN: 152036 Hom.: 53633 Cov.: 32

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.837 AC: 127380 AN: 152154 Hom.: 53684 Cov.: 32 AF XY: 0.838 AC XY: 62358 AN XY: 74406

Gnomad4 AFR AF: 0.919

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.807

Alfa AF: 0.807 Hom.: 6758

Bravo AF: 0.844

Asia WGS AF: 0.954 AC: 3311 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.6
DANN	Benign	0.69

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: rs2317011; hg19: chr2-236821648;