rs5844420

Variant names:

• chr22-20425735-G-GC
• rs5844420
• NM_182895.5:c.2240dupG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP6_Very_Strong

The NM_182895.5(SCARF2):​c.2240dupG​(p.Gly749ArgfsTer25) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G747G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCARF2 NM_182895.5 frameshift
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.399
• Publications: 9 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

ENSG00000305663 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 22-20425735-G-GC is Benign according to our data. Variant chr22-20425735-G-GC is described in ClinVar as Benign. ClinVar VariationId is 403414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.2240dupG	p.Gly749ArgfsTer25	frameshift	Exon 11 of 11	NP_878315.2	Q96GP6-2
	SCARF2	NM_153334.7		c.2255dupG	p.Gly754ArgfsTer25	frameshift	Exon 11 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.2240dupG	p.Gly749ArgfsTer25	frameshift	Exon 11 of 11	ENSP00000477564.2	Q96GP6-2
	SCARF2	ENST00000623402.1	TSL:1	c.2255dupG	p.Gly754ArgfsTer25	frameshift	Exon 11 of 11	ENSP00000485276.1	Q96GP6-1
	SCARF2	ENST00000925309.1		c.2369dupG	p.Gly792ArgfsTer25	frameshift	Exon 11 of 11	ENSP00000595368.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 1.00 AC: 12 AN: 12 AF XY: 1.00

Gnomad NFE exome AF: 1.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 1.00 Hom.: 2224

Asia WGS AF: 0.998 AC: 3111 AN: 3116

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40

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

Other links and lift over

dbSNP: rs5844420; hg19: chr22-20780024; COSMIC: COSV56731664; COSMIC: COSV56731664;