10-100943677-T-C

Variant summary

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

The NM_018121.4(SLF2):c.2655-349T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 165,596 control chromosomes in the GnomAD database, including 6,373 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 0.26 (6006 hom., cov: 32)
  • Exomes 𝑓: 0.21 (367 hom.)
• Consequence: SLF2 NM_018121.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLF2	NM_018121.4	c.2655-349T>C		intron_variant		ENST00000238961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLF2	ENST00000238961.9	c.2655-349T>C		intron_variant		1	NM_018121.4	P2
SLF2	ENST00000370269.3	c.2655-349T>C		intron_variant		1		A2
SLF2	ENST00000481654.1	n.24T>C		non_coding_transcript_exon_variant	1/2	2
SLF2	ENST00000649226.1	c.*686-349T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39884 AN: 151986 Hom.: 5995 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.209 AC: 2824 AN: 13492 Hom.: 367 Cov.: 0 AF XY: 0.210 AC XY: 1441 AN XY: 6876

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.588

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.262 AC: 39924 AN: 152104 Hom.: 6006 Cov.: 32 AF XY: 0.265 AC XY: 19688 AN XY: 74348

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.247

Alfa AF: 0.0953 Hom.: 129

Bravo AF: 0.279

Asia WGS AF: 0.428 AC: 1486 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.1
Dann	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs10883565; hg19: chr10-102703434;