chr2-159324908-G-C

Variant names:

• chr2-159324908-G-C
• rs1226362424
• NM_013450.4:c.6256C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013450.4(BAZ2B):​c.6256C>G​(p.Leu2086Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,409,464 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L2086P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: BAZ2B NM_013450.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.6256C>G	p.Leu2086Val	missense	Exon 36 of 37	NP_038478.2	Q9UIF8-1
	BAZ2B	NM_001329857.2		c.6199C>G	p.Leu2067Val	missense	Exon 36 of 37	NP_001316786.1
	BAZ2B	NM_001329858.2		c.6181C>G	p.Leu2061Val	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.6256C>G	p.Leu2086Val	missense	Exon 36 of 37	ENSP00000376534.2	Q9UIF8-1
	BAZ2B	ENST00000392782.5	TSL:1	c.6148C>G	p.Leu2050Val	missense	Exon 35 of 36	ENSP00000376533.1	Q9UIF8-5
	BAZ2B	ENST00000911534.1		c.6256C>G	p.Leu2086Val	missense	Exon 37 of 38	ENSP00000581593.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1409464 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 700160

African (AFR) AF: 0.00 AC: 0 AN: 29806

American (AMR) AF: 0.00 AC: 0 AN: 32928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25062

East Asian (EAS) AF: 0.00 AC: 0 AN: 35592

South Asian (SAS) AF: 0.00 AC: 0 AN: 75936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1093222

Other (OTH) AF: 0.00 AC: 0 AN: 58294

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.30
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.20
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.67		Loss of stability (P = 0.334)
MVP		0.27
MPC		0.28
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.39
gMVP		0.49
Mutation Taster		=77/23	polymorphism

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: rs1226362424; hg19: chr2-160181419;