10-100924001-G-GA

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_018121.4(SLF2):c.1006dup(p.Arg336LysfsTer27) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLF2 NM_018121.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.75

Genes affected

SLF2 (HGNC:17814): (SMC5-SMC6 complex localization factor 2) Enables ubiquitin protein ligase binding activity. Involved in several processes, including positive regulation of cellular component organization; positive regulation of double-strand break repair; and protein localization to site of double-strand break. Located in chromatin; nucleoplasm; and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-100924001-G-GA is Pathogenic according to our data. Variant chr10-100924001-G-GA is described in ClinVar as [Pathogenic]. Clinvar id is 2443709.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLF2	NM_018121.4	c.1006dup	p.Arg336LysfsTer27	frameshift_variant	5/20	ENST00000238961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLF2	ENST00000238961.9	c.1006dup	p.Arg336LysfsTer27	frameshift_variant	5/20	1	NM_018121.4	P2
SLF2	ENST00000370269.3	c.1006dup	p.Arg336LysfsTer27	frameshift_variant	5/19	1		A2
SLF2	ENST00000370271.7	c.1006dup	p.Arg336LysfsTer27	frameshift_variant	5/6	1
SLF2	ENST00000649226.1	c.1006dup	p.Arg336LysfsTer27	frameshift_variant, NMD_transcript_variant	5/21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Atelis syndrome 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: chr10-102683758;