12-57731209-T-G

Variant names:

• chr12-57731209-T-G
• rs10877011
• NM_001122772.3:c.2145+157A>C

Variant summary

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

The NM_001122772.3(AGAP2):​c.2145+157A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,046 control chromosomes in the GnomAD database, including 7,219 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 0.28 (7219 hom., cov: 32)
• Consequence: AGAP2 NM_001122772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841
• Publications: 37 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122772.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP2	NM_001122772.3	MANE Select	c.2145+157A>C		intron	N/A	NP_001116244.1
	AGAP2	NM_014770.4		c.1137+157A>C		intron	N/A	NP_055585.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP2	ENST00000547588.6	TSL:1 MANE Select	c.2145+157A>C		intron	N/A	ENSP00000449241.1
	AGAP2	ENST00000257897.7	TSL:1	c.1137+157A>C		intron	N/A	ENSP00000257897.3
	AGAP2	ENST00000328568.9	TSL:5	c.1734+157A>C		intron	N/A	ENSP00000328160.4

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42245 AN: 151928 Hom.: 7219 Cov.: 32

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.278 AC: 42248 AN: 152046 Hom.: 7219 Cov.: 32 AF XY: 0.285 AC XY: 21157 AN XY: 74336

African (AFR) AF: 0.0963 AC: 3997 AN: 41496

American (AMR) AF: 0.251 AC: 3828 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 984 AN: 3464

East Asian (EAS) AF: 0.631 AC: 3257 AN: 5160

South Asian (SAS) AF: 0.499 AC: 2402 AN: 4818

European-Finnish (FIN) AF: 0.390 AC: 4124 AN: 10582

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22730 AN: 67936

Other (OTH) AF: 0.252 AC: 531 AN: 2110

Alfa AF: 0.314 Hom.: 24538

Bravo AF: 0.257

Asia WGS AF: 0.495 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.7
DANN	Benign	0.85
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10877011; hg19: chr12-58124992;