rs2273102

Variant names:

• chr20-48972585-T-C
• rs2273102
• NM_006420.3:c.1525+160T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006420.3(ARFGEF2):​c.1525+160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,076 control chromosomes in the GnomAD database, including 7,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.31 (7384 hom., cov: 32)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.747
• Publications: 7 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: DEFINITIVE, 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 20-48972585-T-C is Benign according to our data. Variant chr20-48972585-T-C is described in ClinVar as Benign. ClinVar VariationId is 678157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 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.1525+160T>C		intron	N/A	NP_006411.2	Q9Y6D5
	ARFGEF2	NM_001410846.1		c.1522+160T>C		intron	N/A	NP_001397775.1	A0A7P0T7Z2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFGEF2	ENST00000371917.5	TSL:1 MANE Select	c.1525+160T>C		intron	N/A	ENSP00000360985.4	Q9Y6D5
	ARFGEF2	ENST00000679436.1		c.1522+160T>C		intron	N/A	ENSP00000504888.1	A0A7P0T7Z2
	ARFGEF2	ENST00000939861.1		c.1519+160T>C		intron	N/A	ENSP00000609920.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46351 AN: 151958 Hom.: 7363 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.305 AC: 46415 AN: 152076 Hom.: 7384 Cov.: 32 AF XY: 0.313 AC XY: 23243 AN XY: 74342

African (AFR) AF: 0.363 AC: 15056 AN: 41470

American (AMR) AF: 0.391 AC: 5965 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 837 AN: 3466

East Asian (EAS) AF: 0.473 AC: 2445 AN: 5164

South Asian (SAS) AF: 0.349 AC: 1679 AN: 4808

European-Finnish (FIN) AF: 0.258 AC: 2730 AN: 10584

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16825 AN: 68000

Other (OTH) AF: 0.316 AC: 669 AN: 2114

Alfa AF: 0.272 Hom.: 3301

Bravo AF: 0.321

Asia WGS AF: 0.395 AC: 1375 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.62
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2273102; hg19: chr20-47589122;