2-159325791-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013450.4(BAZ2B):c.6071G>A(p.Ser2024Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,606,358 control chromosomes in the GnomAD database, including 41,452 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (4439 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37013 hom.)
• Consequence: BAZ2B NM_013450.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.02

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001219511).
• BP6: Variant 2-159325791-C-T is Benign according to our data. Variant chr2-159325791-C-T is described in ClinVar as [Benign]. Clinvar id is 3056167.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAZ2B	NM_013450.4	c.6071G>A	p.Ser2024Asn	missense_variant	35/37	ENST00000392783.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAZ2B	ENST00000392783.7	c.6071G>A	p.Ser2024Asn	missense_variant	35/37	5	NM_013450.4	P1
BAZ2B	ENST00000392782.5	c.5963G>A	p.Ser1988Asn	missense_variant	34/36	1
BAZ2B	ENST00000474437.1	n.611G>A		non_coding_transcript_exon_variant	4/4	3
BAZ2B	ENST00000548440.1	n.585G>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36256 AN: 151818 Hom.: 4432 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.251

GnomAD3 exomes AF: 0.222 AC: 54118 AN: 243724 Hom.: 6255 AF XY: 0.226 AC XY: 29856 AN XY: 132206

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.194

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.233

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.223 AC: 324086 AN: 1454422 Hom.: 37013 Cov.: 33 AF XY: 0.224 AC XY: 161927 AN XY: 723164

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.239 AC: 36297 AN: 151936 Hom.: 4439 Cov.: 32 AF XY: 0.240 AC XY: 17855 AN XY: 74272

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.251

Alfa AF: 0.225 Hom.: 8918

Bravo AF: 0.237

TwinsUK AF: 0.230 AC: 853

ALSPAC AF: 0.213 AC: 821

ESP6500AA AF: 0.284 AC: 1037

ESP6500EA AF: 0.219 AC: 1786

ExAC AF: 0.230 AC: 27834

Asia WGS AF: 0.247 AC: 858 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

BAZ2B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	22
Dann	Benign	0.95
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D
MetaRNN	Benign	0.0012	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.047	P;P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.075
Sift	Benign	0.090	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.76	P;B
Vest4		0.093
MPC		0.038
ClinPred		0.011	T
GERP RS		5.8
Varity_R		0.091
gMVP		0.31

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

Other links and lift over

dbSNP: rs415793; hg19: chr2-160182302; COSMIC: COSV58596050;