chr2-235494853-A-G

Variant names:

• chr2-235494853-A-G
• rs200114461
• NM_001037131.3:c.163+4A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001037131.3(AGAP1):​c.163+4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,411,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: AGAP1 NM_001037131.3 splice_region, intron
• Scores: Splicing: ADA: 0.9997
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP1	NM_001037131.3	c.163+4A>G		splice_region_variant, intron_variant	Intron 1 of 17	ENST00000304032.13	NP_001032208.1
AGAP1	NM_014914.5	c.163+4A>G		splice_region_variant, intron_variant	Intron 1 of 16		NP_055729.2
AGAP1	NM_001244888.2	c.163+4A>G		splice_region_variant, intron_variant	Intron 1 of 9		NP_001231817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP1	ENST00000304032.13	c.163+4A>G		splice_region_variant, intron_variant	Intron 1 of 17	5	NM_001037131.3	ENSP00000307634.7

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000472 AC: 1 AN: 211798 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000103

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1411770 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 702362

African (AFR) AF: 0.00 AC: 0 AN: 29212

American (AMR) AF: 0.00 AC: 0 AN: 39458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24430

East Asian (EAS) AF: 0.00 AC: 0 AN: 33708

South Asian (SAS) AF: 0.00 AC: 0 AN: 82298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 9.20e-7 AC: 1 AN: 1086822

Other (OTH) AF: 0.00 AC: 0 AN: 57920

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.96
PhyloP100		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.90
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs200114461; hg19: chr2-236403497;