20-48984729-G-T

Position:

• chr20-48984729-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006420.3(ARFGEF2):​c.1959G>T​(p.Leu653=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARFGEF2 NM_006420.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.5177
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451

Genes affected

ARFGEF2 (HGNC:15853): (ADP ribosylation factor guanine nucleotide exchange factor 2) ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFGEF2	NM_006420.3	c.1959G>T	p.Leu653=	splice_region_variant, synonymous_variant	15/39	ENST00000371917.5	NP_006411.2
ARFGEF2	NM_001410846.1	c.1956G>T	p.Leu652=	splice_region_variant, synonymous_variant	15/39		NP_001397775.1
ARFGEF2	XM_047439832.1	c.1395G>T	p.Leu465=	splice_region_variant, synonymous_variant	13/37		XP_047295788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF2	ENST00000371917.5	c.1959G>T	p.Leu653=	splice_region_variant, synonymous_variant	15/39	1	NM_006420.3	ENSP00000360985	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.52
dbscSNV1_RF	Benign	0.54
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.47		Position offset: -43

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

Publications

LitVar

Other links and lift over

dbSNP: rs200238031; hg19: chr20-47601266;