18-47225867-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278063.4(SKOR2):c.2917+4592C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,984 control chromosomes in the GnomAD database, including 30,045 homozygotes. 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: 𝑓 0.62 (30045 hom., cov: 30)
• Consequence: SKOR2 NM_001278063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655

Genes affected

SKOR2 (HGNC:32695): (SKI family transcriptional corepressor 2) Enables SMAD binding activity and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transforming growth factor beta receptor signaling pathway. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKOR2	NM_001278063.4	c.2917+4592C>G		intron_variant		ENST00000425639.3
SKOR2	XM_047437757.1	c.2917+4592C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKOR2	ENST00000425639.3	c.2917+4592C>G		intron_variant		5	NM_001278063.4	P1
SKOR2	ENST00000620245.4	c.2917+4592C>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94600 AN: 151864 Hom.: 29999 Cov.: 30

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.619

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.623 AC: 94707 AN: 151984 Hom.: 30045 Cov.: 30 AF XY: 0.621 AC XY: 46144 AN XY: 74256

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.623

Alfa AF: 0.560 Hom.: 11967

Bravo AF: 0.627

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.2
Dann	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1398217; hg19: chr18-44752238;