rs12307841

Variant names:

• chr12-57731655-T-C
• rs12307841
• NM_001122772.3:c.1954-13A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PP3_Moderate BA1

The NM_001122772.3(AGAP2):​c.1954-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,850 control chromosomes in the GnomAD database, including 13,334 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 0.10 (1104 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12230 hom.)
• Consequence: AGAP2 NM_001122772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 18 publications found

Genes affected

AGAP2 (HGNC:16921): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 2) The protein encoded by this gene belongs to the centaurin gamma-like family. It mediates anti-apoptotic effects of nerve growth factor by activating nuclear phosphoinositide 3-kinase. It is overexpressed in cancer cells, and promotes cancer cell invasion. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP2	NM_001122772.3	c.1954-13A>G		intron_variant	Intron 8 of 18	ENST00000547588.6	NP_001116244.1
AGAP2	NM_014770.4	c.946-13A>G		intron_variant	Intron 8 of 17		NP_055585.1
AGAP2	XM_005268625.4	c.1954-13A>G		intron_variant	Intron 8 of 17		XP_005268682.1
AGAP2	XM_005268626.3	c.946-13A>G		intron_variant	Intron 8 of 18		XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000547588.6	c.1954-13A>G		intron_variant	Intron 8 of 18	1	NM_001122772.3	ENSP00000449241.1
AGAP2	ENST00000257897.7	c.946-13A>G		intron_variant	Intron 8 of 17	1		ENSP00000257897.3
AGAP2	ENST00000328568.9	c.1543-13A>G		intron_variant	Intron 8 of 17	5		ENSP00000328160.4
AGAP2	ENST00000549129.1	c.22-13A>G		intron_variant	Intron 1 of 4	3		ENSP00000446683.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15816 AN: 151982 Hom.: 1101 Cov.: 32

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0603

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0971

GnomAD2 exomes AF: 0.134 AC: 33565 AN: 251238 AF XY: 0.126

Gnomad AFR exome AF: 0.0298

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.0608

Gnomad EAS exome AF: 0.115

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.123 AC: 180031 AN: 1461750 Hom.: 12230 Cov.: 34 AF XY: 0.121 AC XY: 87942 AN XY: 727172

African (AFR) AF: 0.0265 AC: 886 AN: 33474

American (AMR) AF: 0.282 AC: 12607 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0635 AC: 1659 AN: 26130

East Asian (EAS) AF: 0.0987 AC: 3919 AN: 39700

South Asian (SAS) AF: 0.0924 AC: 7969 AN: 86252

European-Finnish (FIN) AF: 0.146 AC: 7789 AN: 53414

Middle Eastern (MID) AF: 0.0541 AC: 312 AN: 5768

European-Non Finnish (NFE) AF: 0.124 AC: 138179 AN: 1111926

Other (OTH) AF: 0.111 AC: 6711 AN: 60386

GnomAD4 genome AF: 0.104 AC: 15819 AN: 152100 Hom.: 1104 Cov.: 32 AF XY: 0.105 AC XY: 7835 AN XY: 74344

African (AFR) AF: 0.0328 AC: 1362 AN: 41488

American (AMR) AF: 0.209 AC: 3193 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0603 AC: 209 AN: 3466

East Asian (EAS) AF: 0.103 AC: 532 AN: 5178

South Asian (SAS) AF: 0.0948 AC: 456 AN: 4812

European-Finnish (FIN) AF: 0.142 AC: 1497 AN: 10564

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8246 AN: 67992

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.115 Hom.: 281

Bravo AF: 0.109

Asia WGS AF: 0.0820 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Pathogenic	33
DANN	Benign	0.43
PhyloP100		-0.32
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.90		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.90		Position offset: -1

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

Other links and lift over

dbSNP: rs12307841; hg19: chr12-58125438; COSMIC: COSV57727342; COSMIC: COSV57727342;