2-236049178-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037131.3(AGAP1):​c.2011G>C​(p.Val671Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V671I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: AGAP1 NM_001037131.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042730957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP1	NM_001037131.3	c.2011G>C	p.Val671Leu	missense_variant	Exon 16 of 18	ENST00000304032.13	NP_001032208.1
AGAP1	NM_014914.5	c.1852G>C	p.Val618Leu	missense_variant	Exon 15 of 17		NP_055729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP1	ENST00000304032.13	c.2011G>C	p.Val671Leu	missense_variant	Exon 16 of 18	5	NM_001037131.3	ENSP00000307634.7

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152072 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 55

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152072 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74272

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.1
DANN	Benign	0.74
DEOGEN2	Benign	0.034	.;T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.52	T;T;T;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.043	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.64	.;N;.;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.74	N;N;N;.;.
REVEL	Benign	0.054
Sift	Benign	0.68	T;T;T;.;.
Sift4G	Benign	0.93	T;T;T;T;T
Polyphen		0.0	B;B;.;.;.
Vest4		0.060
MutPred		0.55		.;Loss of helix (P = 0.0093);.;.;.;
MVP		0.29
MPC		0.40
ClinPred		0.037	T
GERP RS		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.20

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;