2-159318799-T-C

Variant names:

• chr2-159318799-T-C
• rs174230
• ENST00000718451.1:c.6390+1475A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000718451.1(BAZ2B):​c.6390+1475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,140 control chromosomes in the GnomAD database, including 61,337 homozygotes. 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: 𝑓 0.89 (61337 hom., cov: 31)
• Consequence: BAZ2B ENST00000718451.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000718451.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAZ2B	NM_013450.4	MANE Select	c.*1466A>G		downstream_gene	N/A	NP_038478.2	Q9UIF8-1
	BAZ2B	NM_001329857.2		c.*1466A>G		downstream_gene	N/A	NP_001316786.1
	BAZ2B	NM_001329858.2		c.*1466A>G		downstream_gene	N/A	NP_001316787.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAZ2B	ENST00000718451.1		c.6390+1475A>G		intron	N/A	ENSP00000520831.1	A0ABB0MVI5
	BAZ2B	ENST00000392783.7	TSL:5 MANE Select	c.*1466A>G		downstream_gene	N/A	ENSP00000376534.2	Q9UIF8-1
	BAZ2B	ENST00000392782.5	TSL:1	c.*1466A>G		downstream_gene	N/A	ENSP00000376533.1	Q9UIF8-5

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134683 AN: 152022 Hom.: 61288 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.916

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.886 AC: 134785 AN: 152140 Hom.: 61337 Cov.: 31 AF XY: 0.889 AC XY: 66105 AN XY: 74378

African (AFR) AF: 0.652 AC: 27011 AN: 41410

American (AMR) AF: 0.959 AC: 14676 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3430 AN: 3472

East Asian (EAS) AF: 0.869 AC: 4499 AN: 5178

South Asian (SAS) AF: 0.933 AC: 4502 AN: 4826

European-Finnish (FIN) AF: 0.980 AC: 10403 AN: 10610

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.988 AC: 67206 AN: 68032

Other (OTH) AF: 0.915 AC: 1931 AN: 2110

Alfa AF: 0.948 Hom.: 175210

Bravo AF: 0.874

Asia WGS AF: 0.882 AC: 3066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs174230; hg19: chr2-160175310;