NM_001145451.5:c.2343+2222_2343+2226dupAAAAA

Variant names:

• chr2-38962849-C-CAAAAA
• rs386389985
• NM_001145451.5:c.2343+2222_2343+2226dupAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001145451.5(ARHGEF33):​c.2343+2222_2343+2226dupAAAAA 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 0.0033 (1 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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF33	NM_001145451.5	c.2343+2222_2343+2226dupAAAAA		intron_variant	Intron 16 of 17	ENST00000409978.7	NP_001138923.2
ARHGEF33	NM_001367623.3	c.2343+2222_2343+2226dupAAAAA		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+2202insAAAAA		intron_variant	Intron 16 of 17	5	NM_001145451.5	ENSP00000387020.1

Frequencies

GnomAD3 genomes AF: 0.00328 AC: 174 AN: 53116 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00136

Gnomad AMI AF: 0.00685

Gnomad AMR AF: 0.00325

Gnomad ASJ AF: 0.00165

Gnomad EAS AF: 0.00433

Gnomad SAS AF: 0.00171

Gnomad FIN AF: 0.00244

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00404

Gnomad OTH AF: 0.00325

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

GnomAD4 genome AF: 0.00330 AC: 175 AN: 53108 Hom.: 1 Cov.: 0 AF XY: 0.00311 AC XY: 72 AN XY: 23132

Gnomad4 AFR AF: 0.00136

Gnomad4 AMR AF: 0.00358

Gnomad4 ASJ AF: 0.00165

Gnomad4 EAS AF: 0.00436

Gnomad4 SAS AF: 0.00172

Gnomad4 FIN AF: 0.00244

Gnomad4 NFE AF: 0.00404

Gnomad4 OTH AF: 0.00325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;