2-159322264-C-T

Variant names:

• chr2-159322264-C-T
• rs174226
• NM_013450.4:c.6354-1846G>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.6354-1846G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 151,974 control chromosomes in the GnomAD database, including 27,443 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 0.59 (27443 hom., cov: 32)
• Consequence: BAZ2B NM_013450.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAZ2B	NM_013450.4	MANE Select	c.6354-1846G>A		intron	N/A	NP_038478.2	Q9UIF8-1
	BAZ2B	NM_001329857.2		c.6297-1846G>A		intron	N/A	NP_001316786.1
	BAZ2B	NM_001329858.2		c.6279-1846G>A		intron	N/A	NP_001316787.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAZ2B	ENST00000392783.7	TSL:5 MANE Select	c.6354-1846G>A		intron	N/A	ENSP00000376534.2	Q9UIF8-1
	BAZ2B	ENST00000392782.5	TSL:1	c.6246-1846G>A		intron	N/A	ENSP00000376533.1	Q9UIF8-5
	BAZ2B	ENST00000911534.1		c.6354-1846G>A		intron	N/A	ENSP00000581593.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89008 AN: 151856 Hom.: 27400 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.586 AC: 89102 AN: 151974 Hom.: 27443 Cov.: 32 AF XY: 0.600 AC XY: 44597 AN XY: 74268

African (AFR) AF: 0.696 AC: 28847 AN: 41446

American (AMR) AF: 0.657 AC: 10020 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1939 AN: 3466

East Asian (EAS) AF: 0.947 AC: 4901 AN: 5176

South Asian (SAS) AF: 0.794 AC: 3817 AN: 4810

European-Finnish (FIN) AF: 0.575 AC: 6061 AN: 10544

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31764 AN: 67960

Other (OTH) AF: 0.581 AC: 1229 AN: 2114

Alfa AF: 0.525 Hom.: 2704

Bravo AF: 0.597

Asia WGS AF: 0.857 AC: 2975 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.63
DANN	Benign	0.52
PhyloP100		-0.36
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: rs174226; hg19: chr2-160178775;