rs2034648

chr2-236049178-G-Achr2-236049178-G-Cchr2-236049178-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001037131.3(AGAP1):c.2011G>A(p.Val671Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,613,972 control chromosomes in the GnomAD database, including 257,386 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. V671V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.65 (33870 hom., cov: 33)
  • Exomes 𝑓: 0.55 (223516 hom.)
• Consequence: AGAP1 NM_001037131.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.638

Genes affected

AGAP1 (HGNC:16922): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 1) This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.932896E-7).
• BP6: Variant 2-236049178-G-A is Benign according to our data. Variant chr2-236049178-G-A is described in ClinVar as [Benign]. Clinvar id is 2114466.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGAP1	NM_001037131.3	c.2011G>A	p.Val671Ile	missense_variant	16/18	ENST00000304032.13
AGAP1	NM_014914.5	c.1852G>A	p.Val618Ile	missense_variant	15/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGAP1	ENST00000304032.13	c.2011G>A	p.Val671Ile	missense_variant	16/18	5	NM_001037131.3

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98504 AN: 152022 Hom.: 33807 Cov.: 33

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.614

GnomAD3 exomes AF: 0.604 AC: 151849 AN: 251470 Hom.: 47944 AF XY: 0.586 AC XY: 79654 AN XY: 135910

Gnomad AFR exome AF: 0.884

Gnomad AMR exome AF: 0.774

Gnomad ASJ exome AF: 0.442

Gnomad EAS exome AF: 0.749

Gnomad SAS exome AF: 0.541

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.529

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.547 AC: 798974 AN: 1461830 Hom.: 223516 Cov.: 55 AF XY: 0.544 AC XY: 395968 AN XY: 727218

Gnomad4 AFR exome AF: 0.886

Gnomad4 AMR exome AF: 0.763

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.541

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.522

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.648 AC: 98623 AN: 152142 Hom.: 33870 Cov.: 33 AF XY: 0.648 AC XY: 48172 AN XY: 74372

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.611

Alfa AF: 0.539 Hom.: 40999

Bravo AF: 0.666

TwinsUK AF: 0.516 AC: 1912

ALSPAC AF: 0.528 AC: 2036

ESP6500AA AF: 0.863 AC: 3804

ESP6500EA AF: 0.516 AC: 4439

ExAC AF: 0.602 AC: 73073

Asia WGS AF: 0.638 AC: 2217 AN: 3478

EpiCase AF: 0.518

EpiControl AF: 0.516

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.055
Dann	Benign	0.91
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.19	T;T;T;T;T
MetaRNN	Benign	6.9e-7	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.27	N;N;N;.;.
REVEL	Benign	0.035
Sift	Benign	0.42	T;T;T;.;.
Sift4G	Benign	0.51	T;T;T;T;T
Polyphen		0.0	B;B;.;.;.
Vest4		0.088
MPC		0.33
ClinPred		0.0030	T
GERP RS		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.019
gMVP		0.089

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

Publications

LitVar

Other links and lift over

dbSNP: rs2034648; hg19: chr2-236957822; COSMIC: COSV58326802;