rs2034648

Variant names:

• chr2-236049178-G-A
• rs2034648
• NM_001037131.3:c.2011G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-236049178-G-A
• chr2-236049178-G-C
• chr2-236049178-G-T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). 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
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037131.3. 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
	AGAP1	NM_001037131.3	MANE Select	c.2011G>A	p.Val671Ile	missense	Exon 16 of 18	NP_001032208.1	Q9UPQ3-1
	AGAP1	NM_001436125.1		c.2806G>A	p.Val936Ile	missense	Exon 16 of 18	NP_001423054.1
	AGAP1	NM_001436126.1		c.2647G>A	p.Val883Ile	missense	Exon 15 of 17	NP_001423055.1	E7EUN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGAP1	ENST00000304032.13	TSL:5 MANE Select	c.2011G>A	p.Val671Ile	missense	Exon 16 of 18	ENSP00000307634.7	Q9UPQ3-1
	AGAP1	ENST00000336665.9	TSL:1	c.1852G>A	p.Val618Ile	missense	Exon 15 of 17	ENSP00000338378.5	Q9UPQ3-2
	AGAP1	ENST00000409538.5	TSL:5	c.2647G>A	p.Val883Ile	missense	Exon 15 of 17	ENSP00000386897.1	E7EUN2

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

GnomAD2 exomes AF: 0.604 AC: 151849 AN: 251470 AF XY: 0.586

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 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

African (AFR) AF: 0.886 AC: 29662 AN: 33478

American (AMR) AF: 0.763 AC: 34136 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 11414 AN: 26136

East Asian (EAS) AF: 0.749 AC: 29734 AN: 39698

South Asian (SAS) AF: 0.541 AC: 46642 AN: 86258

European-Finnish (FIN) AF: 0.557 AC: 29770 AN: 53418

Middle Eastern (MID) AF: 0.525 AC: 3028 AN: 5768

European-Non Finnish (NFE) AF: 0.522 AC: 580863 AN: 1111956

Other (OTH) AF: 0.558 AC: 33725 AN: 60394

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

African (AFR) AF: 0.877 AC: 36402 AN: 41512

American (AMR) AF: 0.678 AC: 10363 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1584 AN: 3470

East Asian (EAS) AF: 0.746 AC: 3859 AN: 5170

South Asian (SAS) AF: 0.537 AC: 2591 AN: 4824

European-Finnish (FIN) AF: 0.568 AC: 6009 AN: 10570

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36043 AN: 67996

Other (OTH) AF: 0.611 AC: 1288 AN: 2108

Alfa AF: 0.557 Hom.: 63439

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

ClinVar submissions

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
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.055
DANN	Benign	0.91
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	6.9e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.64
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.035
Sift	Benign	0.42	T
Sift4G	Benign	0.51	T
Polyphen		0.0	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
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: rs2034648; hg19: chr2-236957822; COSMIC: COSV58326802;