chr2-159548987-C-T

Variant names:

• chr2-159548987-C-T
• rs10489997
• NM_013450.4:c.-3+6836G>A

Variant summary

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

The NM_013450.4(BAZ2B):​c.-3+6836G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,016 control chromosomes in the GnomAD database, including 9,668 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 0.32 (9668 hom., cov: 32)
• Consequence: BAZ2B NM_013450.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013450.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAZ2B	NM_013450.4	MANE Select	c.-3+6836G>A		intron	N/A	NP_038478.2
	BAZ2B	NM_001329857.2		c.-3+6836G>A		intron	N/A	NP_001316786.1
	BAZ2B	NM_001329858.2		c.-3+6836G>A		intron	N/A	NP_001316787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAZ2B	ENST00000392783.7	TSL:5 MANE Select	c.-3+6836G>A		intron	N/A	ENSP00000376534.2
	BAZ2B	ENST00000392782.5	TSL:1	c.-3+6836G>A		intron	N/A	ENSP00000376533.1
	BAZ2B	ENST00000483316.1	TSL:1	n.252+6836G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48395 AN: 151898 Hom.: 9666 Cov.: 32

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.318 AC: 48413 AN: 152016 Hom.: 9668 Cov.: 32 AF XY: 0.318 AC XY: 23612 AN XY: 74304

African (AFR) AF: 0.0829 AC: 3440 AN: 41486

American (AMR) AF: 0.441 AC: 6721 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3462

East Asian (EAS) AF: 0.261 AC: 1347 AN: 5166

South Asian (SAS) AF: 0.190 AC: 915 AN: 4826

European-Finnish (FIN) AF: 0.466 AC: 4916 AN: 10552

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28984 AN: 67958

Other (OTH) AF: 0.354 AC: 748 AN: 2114

Alfa AF: 0.387 Hom.: 49427

Bravo AF: 0.311

Asia WGS AF: 0.241 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.62
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10489997; hg19: chr2-160405498;