rs754436179

Variant names:

• chr22-20425421-C-A
• rs754436179
• NM_182895.5:c.2555G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-20425421-C-A
• chr22-20425421-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182895.5(SCARF2):​c.2555G>T​(p.Arg852Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000781 in 1,279,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R852Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: SCARF2 NM_182895.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29
• Publications: 0 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 Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000305663 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19569206).

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.2555G>T	p.Arg852Leu	missense	Exon 11 of 11	NP_878315.2	Q96GP6-2
	SCARF2	NM_153334.7		c.2570G>T	p.Arg857Leu	missense	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.2555G>T	p.Arg852Leu	missense	Exon 11 of 11	ENSP00000477564.2	Q96GP6-2
	SCARF2	ENST00000623402.1	TSL:1	c.2570G>T	p.Arg857Leu	missense	Exon 11 of 11	ENSP00000485276.1	Q96GP6-1
	SCARF2	ENST00000925309.1		c.2684G>T	p.Arg895Leu	missense	Exon 11 of 11	ENSP00000595368.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000163 AC: 2 AN: 122408 AF XY: 0.0000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000192

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.81e-7 AC: 1 AN: 1279836 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 629070

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26730

American (AMR) AF: 0.00 AC: 0 AN: 26104

Ashkenazi Jewish (ASJ) AF: 0.0000480 AC: 1 AN: 20812

East Asian (EAS) AF: 0.00 AC: 0 AN: 30846

South Asian (SAS) AF: 0.00 AC: 0 AN: 64872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4202

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1022944

Other (OTH) AF: 0.00 AC: 0 AN: 51778

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.3
PrimateAI	Pathogenic	0.91	D
Sift4G	Uncertain	0.030	D
Vest4		0.52
MutPred		0.32		Loss of MoRF binding (P = 0.0527)
MVP		0.13
ClinPred		0.72	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.092
gMVP		0.29
Mutation Taster		=84/16	polymorphism

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: rs754436179; hg19: chr22-20779711; COSMIC: COSV56732542; COSMIC: COSV56732542;