rs6019566

Variant names:

• chr20-48974545-C-A
• rs6019566
• NM_006420.3:c.1666-221C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-48974545-C-A
• chr20-48974545-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006420.3(ARFGEF2):​c.1666-221C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,920 control chromosomes in the GnomAD database, including 1,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1688 hom., cov: 31)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.109
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 20-48974545-C-A is Benign according to our data. Variant chr20-48974545-C-A is described in ClinVar as Benign. ClinVar VariationId is 679355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF2	NM_006420.3	MANE Select	c.1666-221C>A		intron	N/A	NP_006411.2
	ARFGEF2	NM_001410846.1		c.1663-221C>A		intron	N/A	NP_001397775.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF2	ENST00000371917.5	TSL:1 MANE Select	c.1666-221C>A		intron	N/A	ENSP00000360985.4
	ARFGEF2	ENST00000679436.1		c.1663-221C>A		intron	N/A	ENSP00000504888.1
	ARFGEF2	ENST00000939861.1		c.1660-221C>A		intron	N/A	ENSP00000609920.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19100 AN: 151802 Hom.: 1683 Cov.: 31

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.126 AC: 19125 AN: 151920 Hom.: 1688 Cov.: 31 AF XY: 0.135 AC XY: 10000 AN XY: 74220

African (AFR) AF: 0.0588 AC: 2437 AN: 41442

American (AMR) AF: 0.251 AC: 3826 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1881 AN: 5154

South Asian (SAS) AF: 0.249 AC: 1196 AN: 4812

European-Finnish (FIN) AF: 0.147 AC: 1549 AN: 10516

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7639 AN: 67950

Other (OTH) AF: 0.136 AC: 286 AN: 2108

Alfa AF: 0.114 Hom.: 1619

Bravo AF: 0.133

Asia WGS AF: 0.268 AC: 933 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.8
DANN	Benign	0.67
PhyloP100		0.11
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: rs6019566; hg19: chr20-47591082;