12-57723862-T-C

Position:

• chr12-57723862-T-C

Variant summary

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

The NM_014770.4(AGAP2):​c.*2690A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,054 control chromosomes in the GnomAD database, including 8,510 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 0.31 (8509 hom., cov: 32)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: AGAP2 NM_014770.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256

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]

OS9 (HGNC:16994): (OS9 endoplasmic reticulum lectin) This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGAP2	NM_014770.4	c.*2690A>G		3_prime_UTR_variant	18/18		NP_055585.1
AGAP2	XM_005268625.4	c.*2690A>G		3_prime_UTR_variant	18/18		XP_005268682.1
AGAP2	XM_005268626.3	c.*2690A>G		3_prime_UTR_variant	19/19		XP_005268683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGAP2	ENST00000257897	c.*2690A>G		3_prime_UTR_variant	18/18	1		ENSP00000257897.3
OS9	ENST00000700670.1	c.286+2994T>C		intron_variant				ENSP00000515138.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46737 AN: 151928 Hom.: 8505 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.375 AC XY: 3 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.308 AC: 46765 AN: 152046 Hom.: 8509 Cov.: 32 AF XY: 0.316 AC XY: 23468 AN XY: 74306

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.289

Alfa AF: 0.345 Hom.: 13066

Bravo AF: 0.283

Asia WGS AF: 0.541 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.5
DANN	Benign	0.89

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: rs701008; hg19: chr12-58117645;