chr2-159325772-G-T

Variant names:

• chr2-159325772-G-T
• NM_013450.4:c.6090C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013450.4(BAZ2B):​c.6090C>A​(p.Asn2030Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BAZ2B NM_013450.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.946
• 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_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03682068).

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.6090C>A	p.Asn2030Lys	missense	Exon 35 of 37	NP_038478.2	Q9UIF8-1
	BAZ2B	NM_001329857.2		c.6033C>A	p.Asn2011Lys	missense	Exon 35 of 37	NP_001316786.1
	BAZ2B	NM_001329858.2		c.6015C>A	p.Asn2005Lys	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.6090C>A	p.Asn2030Lys	missense	Exon 35 of 37	ENSP00000376534.2	Q9UIF8-1
	BAZ2B	ENST00000392782.5	TSL:1	c.5982C>A	p.Asn1994Lys	missense	Exon 34 of 36	ENSP00000376533.1	Q9UIF8-5
	BAZ2B	ENST00000911534.1		c.6090C>A	p.Asn2030Lys	missense	Exon 36 of 38	ENSP00000581593.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451620 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721566

African (AFR) AF: 0.00 AC: 0 AN: 32566

American (AMR) AF: 0.00 AC: 0 AN: 42260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39388

South Asian (SAS) AF: 0.00 AC: 0 AN: 82724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109670

Other (OTH) AF: 0.00 AC: 0 AN: 60042

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.089
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.95
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.18
Sift	Benign	0.55	T
Sift4G	Benign	0.91	T
Polyphen		0.0	B
Vest4		0.074
MutPred		0.23		Loss of loop (P = 0.0128)
MVP		0.11
MPC		0.042
ClinPred		0.24	T
GERP RS		4.8
Varity_R		0.085
gMVP		0.15
Mutation Taster		=88/12	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

hg19: chr2-160182283;