rs786205883

Variant names:

• chr22-20431414-TCGCAGCGCGCGCCCCAG-T
• rs786205883
• NM_182895.5:c.441_457delCTGGGGCGCGCGCTGCG

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_182895.5(SCARF2):​c.441_457delCTGGGGCGCGCGCTGCG​(p.Trp148AlafsTer20) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCARF2 NM_182895.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.54
• Publications: 1 publications found

Genes affected

SCARF2 (HGNC:19869): (scavenger receptor class F member 2) The protein encoded by this gene is similar to SCARF1/SREC-I, a scavenger receptor protein that mediates the binding and degradation of acetylated low density lipoprotein (Ac-LDL). This protein has only little activity of internalizing modified low density lipoproteins (LDL), but it can interact with SCARF1 through its extracellular domain. The association of this protein with SCARF1 is suppressed by the presence of scavenger ligands. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

SCARF2 Gene-Disease associations (from GenCC):

• van den Ende-Gupta syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics

ENSG00000277971 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 22-20431414-TCGCAGCGCGCGCCCCAG-T is Pathogenic according to our data. Variant chr22-20431414-TCGCAGCGCGCGCCCCAG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 190239.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182895.5. 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
	SCARF2	NM_182895.5	MANE Select	c.441_457delCTGGGGCGCGCGCTGCG	p.Trp148AlafsTer20	frameshift	Exon 4 of 11	NP_878315.2	Q96GP6-2
	SCARF2	NM_153334.7		c.441_457delCTGGGGCGCGCGCTGCG	p.Trp148AlafsTer20	frameshift	Exon 4 of 11	NP_699165.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARF2	ENST00000622235.5	TSL:1 MANE Select	c.441_457delCTGGGGCGCGCGCTGCG	p.Trp148AlafsTer20	frameshift	Exon 4 of 11	ENSP00000477564.2	Q96GP6-2
	SCARF2	ENST00000623402.1	TSL:1	c.441_457delCTGGGGCGCGCGCTGCG	p.Trp148AlafsTer20	frameshift	Exon 4 of 11	ENSP00000485276.1	Q96GP6-1
	ENSG00000277971	ENST00000429594.1	TSL:5	n.178-874_178-858delCTGGGGCGCGCGCTGCG		intron	N/A	ENSP00000392268.1	H7BZZ5

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Van den Ende-Gupta syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.5
Mutation Taster		=3/197	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs786205883; hg19: chr22-20785701;