rs6012564

Variant names:

• chr20-48925063-G-A
• rs6012564
• NM_006420.3:c.121+3053G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-48925063-G-A
• chr20-48925063-G-C

Variant summary

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

The NM_006420.3(ARFGEF2):​c.121+3053G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,036 control chromosomes in the GnomAD database, including 29,163 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 0.62 (29163 hom., cov: 32)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 19 publications found

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]

ARFGEF2 Gene-Disease associations (from GenCC):

• periventricular heterotopia with microcephaly, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• periventricular nodular heterotopia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006420.3. 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
	ARFGEF2	NM_006420.3	MANE Select	c.121+3053G>A		intron	N/A	NP_006411.2
	ARFGEF2	NM_001410846.1		c.121+3053G>A		intron	N/A	NP_001397775.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF2	ENST00000371917.5	TSL:1 MANE Select	c.121+3053G>A		intron	N/A	ENSP00000360985.4
	ARFGEF2	ENST00000679436.1		c.121+3053G>A		intron	N/A	ENSP00000504888.1
	ARFGEF2	ENST00000681021.1		c.121+3053G>A		intron	N/A	ENSP00000505972.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93832 AN: 151918 Hom.: 29129 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.618 AC: 93919 AN: 152036 Hom.: 29163 Cov.: 32 AF XY: 0.619 AC XY: 45953 AN XY: 74280

African (AFR) AF: 0.680 AC: 28186 AN: 41470

American (AMR) AF: 0.640 AC: 9778 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1814 AN: 3464

East Asian (EAS) AF: 0.661 AC: 3428 AN: 5186

South Asian (SAS) AF: 0.628 AC: 3023 AN: 4814

European-Finnish (FIN) AF: 0.532 AC: 5604 AN: 10542

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40117 AN: 67962

Other (OTH) AF: 0.592 AC: 1250 AN: 2110

Alfa AF: 0.598 Hom.: 15118

Bravo AF: 0.623

Asia WGS AF: 0.653 AC: 2272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.74
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6012564; hg19: chr20-47541600;