Genetic Variant SLF2:c.2655-349T>C (chr10-100943677-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.112

Publications

10 publications found

Variant links:

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]

SLF2 Gene-Disease associations (from GenCC):

Atelis syndrome 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, PanelApp Australia

SLF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018121.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLF2	NM_018121.4	MANE Select	c.2655-349T>C		intron	N/A	NP_060591.3
	SLF2	NM_001136123.2		c.2655-349T>C		intron	N/A	NP_001129595.1	Q8IX21-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLF2	ENST00000238961.9	TSL:1 MANE Select	c.2655-349T>C	intron	N/A	ENSP00000238961.3	Q8IX21-1
SLF2	ENST00000370269.3	TSL:1	c.2655-349T>C	intron	N/A	ENSP00000359292.3	Q8IX21-2
SLF2	ENST00000855461.1		c.2652-349T>C	intron	N/A	ENSP00000525520.1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39884

AN:

151986

Hom.:

5995

Cov.:

show subpopulations

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.:

AF XY:

0.210

AC XY:

1441

AN XY:

6876

show subpopulations

African (AFR)

AF:

0.351

AC:

168

AN:

478

American (AMR)

AF:

0.377

AC:

116

AN:

308

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

AN:

526

East Asian (EAS)

AF:

0.588

AC:

373

AN:

634

South Asian (SAS)

AF:

0.282

AC:

168

AN:

596

European-Finnish (FIN)

AF:

0.170

AC:

114

AN:

670

Middle Eastern (MID)

AF:

0.200

AC:

AN:

European-Non Finnish (NFE)

AF:

0.175

AC:

1635

AN:

9334

Other (OTH)

AF:

0.185

AC:

164

AN:

886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

112

224

337

449

561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.262

AC:

39924

AN:

152104

Hom.:

6006

Cov.:

AF XY:

0.265

AC XY:

19688

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.353

AC:

14660

AN:

41500

American (AMR)

AF:

0.287

AC:

4383

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

502

AN:

3470

East Asian (EAS)

AF:

0.565

AC:

2915

AN:

5160

South Asian (SAS)

AF:

0.338

AC:

1631

AN:

4822

European-Finnish (FIN)

AF:

0.171

AC:

1813

AN:

10588

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.196

AC:

13314

AN:

67984

Other (OTH)

AF:

0.247

AC:

521

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1422

2844

4267

5689

7111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.1

(source)

DANN

Benign

0.80

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over