chr2-159324847-T-C

Variant names:

• chr2-159324847-T-C
• NM_013450.4:c.6317A>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_013450.4(BAZ2B):​c.6317A>G​(p.Asp2106Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,392,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: BAZ2B NM_013450.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.96

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.6317A>G	p.Asp2106Gly	missense	Exon 36 of 37	NP_038478.2	Q9UIF8-1
	BAZ2B	NM_001329857.2		c.6260A>G	p.Asp2087Gly	missense	Exon 36 of 37	NP_001316786.1
	BAZ2B	NM_001329858.2		c.6242A>G	p.Asp2081Gly	missense	Exon 36 of 37	NP_001316787.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAZ2B	ENST00000392783.7	TSL:5 MANE Select	c.6317A>G	p.Asp2106Gly	missense	Exon 36 of 37	ENSP00000376534.2	Q9UIF8-1
	BAZ2B	ENST00000392782.5	TSL:1	c.6209A>G	p.Asp2070Gly	missense	Exon 35 of 36	ENSP00000376533.1	Q9UIF8-5
	BAZ2B	ENST00000911534.1		c.6317A>G	p.Asp2106Gly	missense	Exon 37 of 38	ENSP00000581593.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1392296 Hom.: 0 Cov.: 29 AF XY: 0.00000145 AC XY: 1 AN XY: 691624

African (AFR) AF: 0.00 AC: 0 AN: 28804

American (AMR) AF: 0.00 AC: 0 AN: 29434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24324

East Asian (EAS) AF: 0.00 AC: 0 AN: 34468

South Asian (SAS) AF: 0.00 AC: 0 AN: 73728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1085810

Other (OTH) AF: 0.00 AC: 0 AN: 57482

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Benign	0.97
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		7.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.86		Gain of MoRF binding (P = 0.0496)
MVP		0.54
MPC		0.31
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.85
gMVP		0.86
Mutation Taster		=9/91	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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

hg19: chr2-160181358;