Genetic Variant BAZ2B:p.Asn2030Lys (chr2-159325772-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013450.4(BAZ2B):c.6090C>A(p.Asn2030Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BAZ2B
NM_013450.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.946

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03682068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAZ2B	NM_013450.4 link	c.6090C>A	p.Asn2030Lys	missense_variant	Exon 35 of 37	ENST00000392783.7	NP_038478.2	Q9UIF8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BAZ2B	ENST00000392783.7 link	c.6090C>A	p.Asn2030Lys	missense_variant	Exon 35 of 37	5	NM_013450.4	ENSP00000376534.2	Q9UIF8-1
BAZ2B	ENST00000392782.5 link	c.5982C>A	p.Asn1994Lys	missense_variant	Exon 34 of 36	1		ENSP00000376533.1	Q9UIF8-5
BAZ2B	ENST00000474437.1 link	n.630C>A		non_coding_transcript_exon_variant	Exon 4 of 4	3
BAZ2B	ENST00000548440.1 link	n.604C>A		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451620

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721566

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Apr 14, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.089

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.86

D;D

M_CAP

Benign

0.0016

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.55

.;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.21

N;N

REVEL

Benign

0.18

Sift

Benign

0.55

T;T

Sift4G

Benign

0.91

T;T

Polyphen

0.0

B;B

Vest4

0.074

MutPred

0.23

.;Loss of loop (P = 0.0128);

MVP

0.11

MPC

0.042

ClinPred

0.24

GERP RS

4.8

Varity_R

0.085

gMVP

0.15

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over