chr18-47225867-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001278063.4(SKOR2):​c.2917+4592C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 152,032 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: 𝑓 0.00019 (0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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>A		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>A		intron	N/A	ENSP00000414750.3
	SKOR2	ENST00000620245.4	TSL:5	c.2917+4592C>A		intron	N/A	ENSP00000483333.1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 151912 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00479

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000480

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

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152032 Hom.: 0 Cov.: 30 AF XY: 0.000269 AC XY: 20 AN XY: 74282

African (AFR) AF: 0.0000482 AC: 2 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5152

South Asian (SAS) AF: 0.00479 AC: 23 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67976

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.00 Hom.: 11967

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.58
PhyloP100		-0.66

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;