dbSNP rs959421: SETDB2:c.1577-99C>G (chr13-49488191-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001160308.3(SETDB2):c.1577-99C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SETDB2
NM_001160308.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.151

Publications

11 publications found

Variant links:

Genes affected

SETDB2 (HGNC:20263): (SET domain bifurcated histone lysine methyltransferase 2) This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

SETDB2 links:

SETDB2-PHF11 (HGNC:):

SETDB2-PHF11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETDB2	NM_001160308.3 link	c.1577-99C>G		intron_variant	Intron 11 of 13	ENST00000611815.2	NP_001153780.1	Q96T68-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SETDB2	ENST00000611815.2 link	c.1577-99C>G	intron_variant	Intron 11 of 13	5	NM_001160308.3	ENSP00000482240.2	Q96T68-2A0A087WYZ9
SETDB2	ENST00000354234.8 link	c.1613-99C>G	intron_variant	Intron 12 of 14	1		ENSP00000346175.5	Q96T68-1
SETDB2	ENST00000317257.12 link	c.1577-99C>G	intron_variant	Intron 10 of 12	1		ENSP00000326477.9	Q96T68-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1308030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

639470

African (AFR)

AF:

0.00

AC:

AN:

29418

American (AMR)

AF:

0.00

AC:

AN:

22556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19222

East Asian (EAS)

AF:

0.00

AC:

AN:

37786

South Asian (SAS)

AF:

0.00

AC:

AN:

61734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3666

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1043898

Other (OTH)

AF:

0.00

AC:

AN:

54046

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

4551

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.3

(source)

DANN

Benign

0.58

PhyloP100

-0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over