Variant 2-159325887-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013450.4(BAZ2B):c.5975T>G(p.Leu1992Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 1,588,828 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 1 hom. )

Consequence

BAZ2B
NM_013450.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38

Variant links:

Genes affected

BAZ2B (HGNC:963): (bromodomain adjacent to zinc finger domain 2B) This gene belongs to the bromodomain gene family. Members of this gene family encode proteins that are integral components of chromatin remodeling complexes. The encoded protein showed strong preference for the activating H3K14Ac mark in a histone peptide screen, suggesting a potential role in transcriptional activation. This gene may be associated with susceptibility to sudden cardiac death (SCD). [provided by RefSeq, Aug 2016]

BAZ2B links:

BAZ2B (HGNC:):

BAZ2B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19321439).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAZ2B	NM_013450.4 linkuse as main transcript	c.5975T>G	p.Leu1992Arg	missense_variant	35/37	ENST00000392783.7	NP_038478.2	Q9UIF8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BAZ2B	ENST00000392783.7 linkuse as main transcript	c.5975T>G	p.Leu1992Arg	missense_variant	35/37	5	NM_013450.4	ENSP00000376534.2	Q9UIF8-1
BAZ2B	ENST00000392782.5 linkuse as main transcript	c.5867T>G	p.Leu1956Arg	missense_variant	34/36	1		ENSP00000376533.1	Q9UIF8-5
BAZ2B	ENST00000474437.1 linkuse as main transcript	n.515T>G		non_coding_transcript_exon_variant	4/4	3
BAZ2B	ENST00000548440.1 linkuse as main transcript	n.489T>G		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000135

AC:

AN:

222894

Hom.:

AF XY:

0.0000165

AC XY:

AN XY:

121264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000284

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000153

AC:

AN:

1436802

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

714142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000541

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000127

Gnomad4 OTH exome

AF:

0.0000505

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152026

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 31, 2024

The c.5975T>G (p.L1992R) alteration is located in exon 35 (coding exon 33) of the BAZ2B gene. This alteration results from a T to G substitution at nucleotide position 5975, causing the leucine (L) at amino acid position 1992 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.033

.;T

Eigen

Benign

-0.0095

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

.;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.14

Sift

Benign

0.16

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.14

B;P

Vest4

0.53

MVP

0.29

MPC

0.063

ClinPred

0.29

GERP RS

5.6

Varity_R

0.20

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over