Variant 20-48921858-GCGGGGCCGTCAGCCCCCGCCGGGC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_006420.3(ARFGEF2):c.-24_-1delGTCAGCCCCCGCCGGGCCGGGGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,503,662 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

ARFGEF2
NM_006420.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.03

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 20-48921858-GCGGGGCCGTCAGCCCCCGCCGGGC-G is Benign according to our data. Variant chr20-48921858-GCGGGGCCGTCAGCCCCCGCCGGGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 418016.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00144 (219/152010) while in subpopulation AFR AF= 0.00427 (177/41500). AF 95% confidence interval is 0.00375. There are 0 homozygotes in gnomad4. There are 103 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
ARFGEF2	NM_006420.3 linkuse as main transcript	c.-24_-1delGTCAGCCCCCGCCGGGCCGGGGCC	5_prime_UTR_variant	1/39	ENST00000371917.5	NP_006411.2	Q9Y6D5Q86TH5Q59FR3
ARFGEF2	NM_001410846.1 linkuse as main transcript	c.-24_-1delGTCAGCCCCCGCCGGGCCGGGGCC	5_prime_UTR_variant	1/39		NP_001397775.1
ARFGEF2	XM_047439832.1 linkuse as main transcript	c.-433_-410delGTCAGCCCCCGCCGGGCCGGGGCC	5_prime_UTR_variant	1/37		XP_047295788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF2	ENST00000371917 linkuse as main transcript	c.-24_-1delGTCAGCCCCCGCCGGGCCGGGGCC		5_prime_UTR_variant	1/39	1	NM_006420.3	ENSP00000360985.4		Q9Y6D5

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

219

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00428

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000383

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000455

AC:

AN:

118654

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

64274

show subpopulations

Gnomad AFR exome

AF:

0.00776

Gnomad AMR exome

AF:

0.0000995

Gnomad ASJ exome

AF:

0.000138

Gnomad EAS exome

AF:

0.000160

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000268

Gnomad NFE exome

AF:

0.000409

Gnomad OTH exome

AF:

0.000612

GnomAD4 exome

AF:

0.000297

AC:

402

AN:

1351652

Hom.:

AF XY:

0.000321

AC XY:

214

AN XY:

666382

show subpopulations

Gnomad4 AFR exome

AF:

0.00485

Gnomad4 AMR exome

AF:

0.000318

Gnomad4 ASJ exome

AF:

0.0000427

Gnomad4 EAS exome

AF:

0.0000657

Gnomad4 SAS exome

AF:

0.0000932

Gnomad4 FIN exome

AF:

0.000294

Gnomad4 NFE exome

AF:

0.000202

Gnomad4 OTH exome

AF:

0.000396

GnomAD4 genome

AF:

0.00144

AC:

219

AN:

152010

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

103

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00427

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.000383

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.00159

Asia WGS

AF:

0.000289

AC:

AN:

3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ARFGEF2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 29, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 25, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over