2-159325798-T-G

Variant names:

• chr2-159325798-T-G
• rs750412559
• NM_013450.4:c.6064A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013450.4(BAZ2B):​c.6064A>C​(p.Thr2022Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2022A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BAZ2B NM_013450.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23178291).

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.6064A>C	p.Thr2022Pro	missense	Exon 35 of 37	NP_038478.2	Q9UIF8-1
	BAZ2B	NM_001329857.2		c.6007A>C	p.Thr2003Pro	missense	Exon 35 of 37	NP_001316786.1
	BAZ2B	NM_001329858.2		c.5989A>C	p.Thr1997Pro	missense	Exon 35 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.6064A>C	p.Thr2022Pro	missense	Exon 35 of 37	ENSP00000376534.2	Q9UIF8-1
	BAZ2B	ENST00000392782.5	TSL:1	c.5956A>C	p.Thr1986Pro	missense	Exon 34 of 36	ENSP00000376533.1	Q9UIF8-5
	BAZ2B	ENST00000911534.1		c.6064A>C	p.Thr2022Pro	missense	Exon 36 of 38	ENSP00000581593.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457754 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724864

African (AFR) AF: 0.00 AC: 0 AN: 33198

American (AMR) AF: 0.00 AC: 0 AN: 44094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39450

South Asian (SAS) AF: 0.00 AC: 0 AN: 84678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110960

Other (OTH) AF: 0.00 AC: 0 AN: 60232

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.19
Sift	Benign	0.19	T
Sift4G	Benign	0.27	T
Polyphen		0.90	P
Vest4		0.29
MutPred		0.23		Loss of helix (P = 0.0237)
MVP		0.37
MPC		0.26
ClinPred		0.87	D
GERP RS		4.5
Varity_R		0.14
gMVP		0.31
Mutation Taster		=84/16	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: rs750412559; hg19: chr2-160182309;