chr18-47225867-G-C

Variant names:

• chr18-47225867-G-C
• rs1398217
• NM_001278063.4:c.2917+4592C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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]

SKOR2 Gene-Disease associations (from GenCC):

• nervous system disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278063.4. 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
	SKOR2	NM_001278063.4	MANE Select	c.2917+4592C>G		intron	N/A	NP_001264992.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKOR2	ENST00000425639.3	TSL:5 MANE Select	c.2917+4592C>G		intron	N/A	ENSP00000414750.3
	SKOR2	ENST00000620245.4	TSL:5	c.2917+4592C>G		intron	N/A	ENSP00000483333.1

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

African (AFR) AF: 0.756 AC: 31362 AN: 41464

American (AMR) AF: 0.573 AC: 8747 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2095 AN: 3468

East Asian (EAS) AF: 0.443 AC: 2283 AN: 5148

South Asian (SAS) AF: 0.551 AC: 2642 AN: 4796

European-Finnish (FIN) AF: 0.635 AC: 6706 AN: 10568

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38783 AN: 67958

Other (OTH) AF: 0.623 AC: 1311 AN: 2106

Alfa AF: 0.560 Hom.: 11967

Bravo AF: 0.627

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.48
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1398217; hg19: chr18-44752238;