NM_001145451.5:c.2343+2226dupA

Variant names:

• chr2-38962849-C-CA
• rs386389985
• NM_001145451.5:c.2343+2226dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001145451.5(ARHGEF33):​c.2343+2226dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.077 (846 hom., cov: 0)
• Consequence: ARHGEF33 NM_001145451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

Genes affected

ARHGEF33 (HGNC:37252): (Rho guanine nucleotide exchange factor 33) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

SOS1 (HGNC:11187): (SOS Ras/Rac guanine nucleotide exchange factor 1) This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF33	NM_001145451.5	c.2343+2226dupA		intron_variant	Intron 16 of 17	ENST00000409978.7	NP_001138923.2
ARHGEF33	NM_001367623.3	c.2343+2226dupA		intron_variant	Intron 16 of 18		NP_001354552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF33	ENST00000409978.7	c.2343+2201_2343+2202insA		intron_variant	Intron 16 of 17	5	NM_001145451.5	ENSP00000387020.1

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 4333 AN: 56156 Hom.: 845 Cov.: 0

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.00408

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.0158

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.0144

Gnomad FIN AF: 0.0266

Gnomad MID AF: 0.0476

Gnomad NFE AF: 0.00551

Gnomad OTH AF: 0.0585

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0773 AC: 4340 AN: 56146 Hom.: 846 Cov.: 0 AF XY: 0.0835 AC XY: 2032 AN XY: 24342

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.0375

Gnomad4 ASJ AF: 0.0158

Gnomad4 EAS AF: 0.0738

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.0266

Gnomad4 NFE AF: 0.00551

Gnomad4 OTH AF: 0.0585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs386389985; hg19: chr2-39189990;