chr2-235494818-C-T

Variant names:

• chr2-235494818-C-T
• rs8178993
• NM_001037131.3:c.132C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001037131.3(AGAP1):​c.132C>T​(p.Asn44Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,579,606 control chromosomes in the GnomAD database, including 749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (54 hom., cov: 29)
  • Exomes 𝑓: 0.028 (695 hom.)
• Consequence: AGAP1 NM_001037131.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.48

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 2-235494818-C-T is Benign according to our data. Variant chr2-235494818-C-T is described in ClinVar as [Benign]. Clinvar id is 2013594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.48 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0202 (3065/151520) while in subpopulation NFE AF = 0.0319 (2159/67760). AF 95% confidence interval is 0.0307. There are 54 homozygotes in GnomAd4. There are 1382 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 54 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP1	NM_001037131.3	c.132C>T	p.Asn44Asn	synonymous_variant	Exon 1 of 18	ENST00000304032.13	NP_001032208.1
AGAP1	NM_014914.5	c.132C>T	p.Asn44Asn	synonymous_variant	Exon 1 of 17		NP_055729.2
AGAP1	NM_001244888.2	c.132C>T	p.Asn44Asn	synonymous_variant	Exon 1 of 10		NP_001231817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGAP1	ENST00000304032.13	c.132C>T	p.Asn44Asn	synonymous_variant	Exon 1 of 18	5	NM_001037131.3	ENSP00000307634.7

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3064 AN: 151414 Hom.: 54 Cov.: 29

Gnomad AFR AF: 0.00600

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0168

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00880

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0283

GnomAD2 exomes AF: 0.0189 AC: 4268 AN: 225286 AF XY: 0.0191

Gnomad AFR exome AF: 0.00500

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.0159

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00779

Gnomad NFE exome AF: 0.0310

Gnomad OTH exome AF: 0.0236

GnomAD4 exome AF: 0.0278 AC: 39712 AN: 1428086 Hom.: 695 Cov.: 32 AF XY: 0.0272 AC XY: 19321 AN XY: 710374

Gnomad4 AFR exome AF: 0.00448 AC: 136 AN: 30390

Gnomad4 AMR exome AF: 0.0162 AC: 668 AN: 41184

Gnomad4 ASJ exome AF: 0.0159 AC: 397 AN: 25030

Gnomad4 EAS exome AF: 0.0000280 AC: 1 AN: 35682

Gnomad4 SAS exome AF: 0.00463 AC: 386 AN: 83368

Gnomad4 FIN exome AF: 0.00963 AC: 509 AN: 52854

Gnomad4 NFE exome AF: 0.0330 AC: 36182 AN: 1095140

Gnomad4 Remaining exome AF: 0.0227 AC: 1335 AN: 58780

GnomAD4 genome AF: 0.0202 AC: 3065 AN: 151520 Hom.: 54 Cov.: 29 AF XY: 0.0187 AC XY: 1382 AN XY: 74078

Gnomad4 AFR AF: 0.00599 AC: 0.00598687 AN: 0.00598687

Gnomad4 AMR AF: 0.0244 AC: 0.024403 AN: 0.024403

Gnomad4 ASJ AF: 0.0168 AC: 0.0167727 AN: 0.0167727

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00478 AC: 0.00477575 AN: 0.00477575

Gnomad4 FIN AF: 0.00880 AC: 0.00880383 AN: 0.00880383

Gnomad4 NFE AF: 0.0319 AC: 0.0318625 AN: 0.0318625

Gnomad4 OTH AF: 0.0280 AC: 0.0279886 AN: 0.0279886

Alfa AF: 0.0257 Hom.: 38

Bravo AF: 0.0217

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

Publications

LitVar

Other links and lift over

dbSNP: rs8178993; hg19: chr2-236403462;