11-47165493-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032389.6(ARFGAP2):c.1555G>A(p.Gly519Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0054 in 1,569,028 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (30 hom.)
• Consequence: ARFGAP2 NM_032389.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.67

Genes affected

ARFGAP2 (HGNC:13504): (ADP ribosylation factor GTPase activating protein 2) Predicted to enable GTPase activator activity. Predicted to be involved in COPI coating of Golgi vesicle. Located in Golgi apparatus; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009077549).
• BP6: Variant 11-47165493-C-T is Benign according to our data. Variant chr11-47165493-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3044117.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARFGAP2	NM_032389.6	c.1555G>A	p.Gly519Ser	missense_variant	16/16	ENST00000524782.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARFGAP2	ENST00000524782.6	c.1555G>A	p.Gly519Ser	missense_variant	16/16	1	NM_032389.6	A1

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 480 AN: 150892 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00403

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00532

Gnomad OTH AF: 0.00145

GnomAD3 exomes AF: 0.00304 AC: 622 AN: 204746 Hom.: 6 AF XY: 0.00299 AC XY: 336 AN XY: 112196

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000205

Gnomad FIN exome AF: 0.00126

Gnomad NFE exome AF: 0.00485

Gnomad OTH exome AF: 0.00486

GnomAD4 exome AF: 0.00564 AC: 7997 AN: 1418020 Hom.: 30 Cov.: 29 AF XY: 0.00542 AC XY: 3826 AN XY: 705474

Gnomad4 AFR exome AF: 0.00118

Gnomad4 AMR exome AF: 0.00319

Gnomad4 ASJ exome AF: 0.0000801

Gnomad4 EAS exome AF: 0.0000541

Gnomad4 SAS exome AF: 0.000236

Gnomad4 FIN exome AF: 0.00156

Gnomad4 NFE exome AF: 0.00681

Gnomad4 OTH exome AF: 0.00529

GnomAD4 genome AF: 0.00317 AC: 479 AN: 151008 Hom.: 4 Cov.: 32 AF XY: 0.00289 AC XY: 213 AN XY: 73742

Gnomad4 AFR AF: 0.00100

Gnomad4 AMR AF: 0.00403

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00105

Gnomad4 NFE AF: 0.00530

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00449 Hom.: 2

Bravo AF: 0.00361

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00558 AC: 48

ExAC AF: 0.00288 AC: 350

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ARFGAP2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 23, 2022

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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	22
Dann	Uncertain	0.99
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.0091	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.58	T
REVEL	Benign	0.094
Sift4G	Benign	0.11	T;T;T
Polyphen		0.98	.;.;D
Vest4		0.35
MVP		0.33
MPC		0.34
ClinPred		0.021	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs142683966; hg19: chr11-47187044;