Genetic Variant SETDB2:n.22delA (chr13-49444704-CA-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000481439.1(SETDB2):n.22delA variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 16037 hom., cov: 0)

Exomes 𝑓: 0.46 ( 119 hom. )

Consequence

SETDB2
ENST00000481439.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETDB2	NM_001160308.3 link	c.-494delA		5_prime_UTR_variant	Exon 1 of 14	ENST00000611815.2	NP_001153780.1	Q96T68-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SETDB2	ENST00000481439.1 link	n.22delA	non_coding_transcript_exon_variant	Exon 1 of 2	1
SETDB2	ENST00000611815.2 link	c.-494delA	5_prime_UTR_variant	Exon 1 of 14	5	NM_001160308.3	ENSP00000482240.2	Q96T68-2A0A087WYZ9
SETDB2	ENST00000354234.8 link	c.-494delA	5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000346175.5	Q96T68-1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65771

AN:

151644

Hom.:

16032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.502

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.470

GnomAD4 exome

AF:

0.460

AC:

440

AN:

956

Hom.:

119

Cov.:

AF XY:

0.425

AC XY:

226

AN XY:

532

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.360

AC:

AN:

150

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.294

AC:

AN:

126

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.511

AC:

325

AN:

636

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.433

AC:

65781

AN:

151762

Hom.:

16037

Cov.:

AF XY:

0.433

AC XY:

32077

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.194

AC:

8035

AN:

41514

American (AMR)

AF:

0.470

AC:

7170

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

1789

AN:

3464

East Asian (EAS)

AF:

0.502

AC:

2576

AN:

5136

South Asian (SAS)

AF:

0.361

AC:

1738

AN:

4820

European-Finnish (FIN)

AF:

0.532

AC:

5578

AN:

10480

Middle Eastern (MID)

AF:

0.541

AC:

158

AN:

292

European-Non Finnish (NFE)

AF:

0.551

AC:

37329

AN:

67786

Other (OTH)

AF:

0.470

AC:

989

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1797

3594

5390

7187

8984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.172

Hom.:

707

Bravo

AF:

0.424

Asia WGS

AF:

0.421

AC:

1462

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.7

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over