18-47232294-G-T

Variant names:

• chr18-47232294-G-T
• rs9304344
• NM_001278063.4:c.2753-1294C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278063.4(SKOR2):​c.2753-1294C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,998 control chromosomes in the GnomAD database, including 11,635 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 0.38 (11635 hom., cov: 32)
• Consequence: SKOR2 NM_001278063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKOR2	NM_001278063.4	c.2753-1294C>A		intron_variant	Intron 4 of 8	ENST00000425639.3	NP_001264992.1
SKOR2	NM_001037802.3	c.850-1130C>A		intron_variant	Intron 3 of 3		NP_001032891.1
SKOR2	XM_047437757.1	c.2753-1294C>A		intron_variant	Intron 3 of 7		XP_047293713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKOR2	ENST00000425639.3	c.2753-1294C>A		intron_variant	Intron 4 of 8	5	NM_001278063.4	ENSP00000414750.3
SKOR2	ENST00000400404.1	c.850-1130C>A		intron_variant	Intron 2 of 2	1		ENSP00000383255.1
SKOR2	ENST00000620245.4	c.2753-1294C>A		intron_variant	Intron 3 of 6	5		ENSP00000483333.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57257 AN: 151880 Hom.: 11634 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.377 AC: 57259 AN: 151998 Hom.: 11635 Cov.: 32 AF XY: 0.379 AC XY: 28153 AN XY: 74284

African (AFR) AF: 0.228 AC: 9436 AN: 41430

American (AMR) AF: 0.399 AC: 6097 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1663 AN: 3468

East Asian (EAS) AF: 0.158 AC: 820 AN: 5184

South Asian (SAS) AF: 0.432 AC: 2080 AN: 4820

European-Finnish (FIN) AF: 0.496 AC: 5239 AN: 10554

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30411 AN: 67948

Other (OTH) AF: 0.389 AC: 820 AN: 2110

Alfa AF: 0.349 Hom.: 2543

Bravo AF: 0.362

Asia WGS AF: 0.270 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.62
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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: rs9304344; hg19: chr18-44758665;