2-38962849-CAAAAAAAAAAA-CAAAA

Variant names:

• chr2-38962849-CAAAAAAA-C
• rs386389985
• NM_001145451.5:c.2343+2220_2343+2226delAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001145451.5(ARHGEF33):​c.2343+2220_2343+2226delAAAAAAA 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 0.0 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF33 NM_001145451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 1 publications found

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]

SOS1 Gene-Disease associations (from GenCC):

• Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Noonan syndrome 4

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp
• fibromatosis, gingival, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary gingival fibromatosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cardiofaciocutaneous syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Costello syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome with multiple lentigines

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145451.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF33	NM_001145451.5	MANE Select	c.2343+2220_2343+2226delAAAAAAA		intron	N/A	NP_001138923.2	A8MVX0-2
	ARHGEF33	NM_001367623.3		c.2343+2220_2343+2226delAAAAAAA		intron	N/A	NP_001354552.1	A8MVX0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF33	ENST00000409978.7	TSL:5 MANE Select	c.2343+2202_2343+2208delAAAAAAA		intron	N/A	ENSP00000387020.1	A8MVX0-2
	SOS1	ENST00000692089.1		c.3400-11_3400-5delTTTTTTT		splice_region intron	N/A	ENSP00000508626.1	A0A8I5QJ77
	ARHGEF33	ENST00000698009.1		c.2487+2202_2487+2208delAAAAAAA		intron	N/A	ENSP00000513494.1	A0A8V8TLC5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 56130 Hom.: 0 Cov.: 0

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

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

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 56122 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 24330

African (AFR) AF: 0.00 AC: 0 AN: 12110

American (AMR) AF: 0.00 AC: 0 AN: 3198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1960

East Asian (EAS) AF: 0.00 AC: 0 AN: 1642

South Asian (SAS) AF: 0.00 AC: 0 AN: 1172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 40

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 34452

Other (OTH) AF: 0.00 AC: 0 AN: 646

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs386389985; hg19: chr2-39189990;