chr22-20425454-G-T

Variant names:

• chr22-20425454-G-T
• NM_182895.5:c.2522C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182895.5(SCARF2):​c.2522C>A​(p.Thr841Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000079 in 1,266,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: SCARF2 NM_182895.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.35

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23538736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARF2	NM_182895.5	c.2522C>A	p.Thr841Asn	missense_variant	Exon 11 of 11	ENST00000622235.5	NP_878315.2
SCARF2	NM_153334.7	c.2537C>A	p.Thr846Asn	missense_variant	Exon 11 of 11		NP_699165.3
SCARF2	XM_047441585.1	c.2636C>A	p.Thr879Asn	missense_variant	Exon 11 of 11		XP_047297541.1
SCARF2	XM_017029065.3	c.*751C>A		3_prime_UTR_variant	Exon 11 of 11		XP_016884554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARF2	ENST00000622235.5	c.2522C>A	p.Thr841Asn	missense_variant	Exon 11 of 11	1	NM_182895.5	ENSP00000477564.2
SCARF2	ENST00000623402.1	c.2537C>A	p.Thr846Asn	missense_variant	Exon 11 of 11	1		ENSP00000485276.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.90e-7 AC: 1 AN: 1266024 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 620962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.84e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.95	D
Sift4G	Benign	0.12	T;T
Vest4		0.41
MVP		0.26
ClinPred		0.92	D
GERP RS		2.6
Varity_R		0.090
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-20779744;