2-38962849-C-CAAAA

Position:

• chr2-38962849-C-CAAAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001145451.5(ARHGEF33):​c.2343+2223_2343+2226dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0027 (3 hom., cov: 0)
• Consequence: ARHGEF33 NM_001145451.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ARHGEF33 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-38962849-C-CAAAA is Benign according to our data. Variant chr2-38962849-C-CAAAA is described in ClinVar as [Benign]. Clinvar id is 3389483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF33	NM_001145451.5	c.2343+2223_2343+2226dupAAAA		intron_variant		ENST00000409978.7	NP_001138923.2
ARHGEF33	NM_001367623.3	c.2343+2223_2343+2226dupAAAA		intron_variant			NP_001354552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF33	ENST00000409978.7	c.2343+2223_2343+2226dupAAAA		intron_variant		5	NM_001145451.5	ENSP00000387020.1

Frequencies

GnomAD3 genomes AF: 0.00274 AC: 153 AN: 55752 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00516

Gnomad AMI AF: 0.00612

Gnomad AMR AF: 0.00313

Gnomad ASJ AF: 0.00205

Gnomad EAS AF: 0.00242

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00971

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00189

Gnomad OTH AF: 0.00310

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

GnomAD4 genome AF: 0.00274 AC: 153 AN: 55744 Hom.: 3 Cov.: 0 AF XY: 0.00265 AC XY: 64 AN XY: 24166

Gnomad4 AFR AF: 0.00515

Gnomad4 AMR AF: 0.00313

Gnomad4 ASJ AF: 0.00205

Gnomad4 EAS AF: 0.00244

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00971

Gnomad4 NFE AF: 0.00189

Gnomad4 OTH AF: 0.00310

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

SOS1: BP4, BS1, BS2 -

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;