chr22-20427438-G-A

Variant names:

• chr22-20427438-G-A
• rs76472118
• NM_182895.5:c.1653C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_182895.5(SCARF2):​c.1653C>T​(p.Asp551Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,614,176 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (48 hom.)
• Consequence: SCARF2 NM_182895.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.62
• Publications: 2 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: G2P, Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000305663 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 22-20427438-G-A is Benign according to our data. Variant chr22-20427438-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 436647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.62 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00452 (689/152348) while in subpopulation SAS AF = 0.0135 (65/4824). AF 95% confidence interval is 0.0108. There are 3 homozygotes in GnomAd4. There are 338 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARF2	NM_182895.5	MANE Select	c.1653C>T	p.Asp551Asp	synonymous	Exon 10 of 11	NP_878315.2
	SCARF2	NM_153334.7		c.1668C>T	p.Asp556Asp	synonymous	Exon 10 of 11	NP_699165.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARF2	ENST00000622235.5	TSL:1 MANE Select	c.1653C>T	p.Asp551Asp	synonymous	Exon 10 of 11	ENSP00000477564.2
	SCARF2	ENST00000623402.1	TSL:1	c.1668C>T	p.Asp556Asp	synonymous	Exon 10 of 11	ENSP00000485276.1
	SCARF2	ENST00000494535.1	TSL:2	n.544C>T		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes AF: 0.00452 AC: 688 AN: 152230 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00907

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00413 AC: 1039 AN: 251366 AF XY: 0.00465

Gnomad AFR exome AF: 0.00886

Gnomad AMR exome AF: 0.00286

Gnomad ASJ exome AF: 0.0131

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000985

Gnomad OTH exome AF: 0.00521

GnomAD4 exome AF: 0.00236 AC: 3451 AN: 1461828 Hom.: 48 Cov.: 32 AF XY: 0.00285 AC XY: 2073 AN XY: 727196

African (AFR) AF: 0.0110 AC: 368 AN: 33478

American (AMR) AF: 0.00347 AC: 155 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 354 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0172 AC: 1487 AN: 86246

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53414

Middle Eastern (MID) AF: 0.00886 AC: 51 AN: 5758

European-Non Finnish (NFE) AF: 0.000696 AC: 774 AN: 1111994

Other (OTH) AF: 0.00426 AC: 257 AN: 60384

GnomAD4 genome AF: 0.00452 AC: 689 AN: 152348 Hom.: 3 Cov.: 33 AF XY: 0.00454 AC XY: 338 AN XY: 74494

African (AFR) AF: 0.00911 AC: 379 AN: 41582

American (AMR) AF: 0.00758 AC: 116 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000853 AC: 58 AN: 68024

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00327 Hom.: 4

Bravo AF: 0.00510

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00136

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Dec 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Oct 15, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Jun 09, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		1.6
Mutation Taster		=99/1	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: rs76472118; hg19: chr22-20781725; COSMIC: COSV107239475; COSMIC: COSV107239475;