22-20425532-G-A

Variant names:

• chr22-20425532-G-A
• rs874100
• NM_182895.5:c.2444C>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.2444C>T​(p.Ala815Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000084 in 1,190,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A815G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: SCARF2 NM_182895.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751
• 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=0.07040274).

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.2444C>T	p.Ala815Val	missense	Exon 11 of 11	NP_878315.2	Q96GP6-2
	SCARF2	NM_153334.7		c.2459C>T	p.Ala820Val	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.2444C>T	p.Ala815Val	missense	Exon 11 of 11	ENSP00000477564.2	Q96GP6-2
	SCARF2	ENST00000623402.1	TSL:1	c.2459C>T	p.Ala820Val	missense	Exon 11 of 11	ENSP00000485276.1	Q96GP6-1
	SCARF2	ENST00000925309.1		c.2573C>T	p.Ala858Val	missense	Exon 11 of 11	ENSP00000595368.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.40e-7 AC: 1 AN: 1190082 Hom.: 0 Cov.: 39 AF XY: 0.00000174 AC XY: 1 AN XY: 575722

⚠️ 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: 24162

American (AMR) AF: 0.00 AC: 0 AN: 11588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16228

East Asian (EAS) AF: 0.00 AC: 0 AN: 28412

South Asian (SAS) AF: 0.00 AC: 0 AN: 48300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 981676

Other (OTH) AF: 0.0000207 AC: 1 AN: 48246

⚠️ 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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.93
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.75
PrimateAI	Uncertain	0.74	T
Sift4G	Benign	0.27	T
Vest4		0.080
MVP		0.055
ClinPred		0.049	T
GERP RS		0.076
Varity_R		0.017
gMVP		0.24
Mutation Taster		=93/7	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: rs874100; hg19: chr22-20779822;