2-159325866-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_013450.4(BAZ2B):c.5996C>G(p.Thr1999Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,595,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: BAZ2B NM_013450.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.13

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.00920856).
• BP6: Variant 2-159325866-G-C is Benign according to our data. Variant chr2-159325866-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3133115.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAZ2B	NM_013450.4	c.5996C>G	p.Thr1999Ser	missense_variant	35/37	ENST00000392783.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAZ2B	ENST00000392783.7	c.5996C>G	p.Thr1999Ser	missense_variant	35/37	5	NM_013450.4	P1
BAZ2B	ENST00000392782.5	c.5888C>G	p.Thr1963Ser	missense_variant	34/36	1
BAZ2B	ENST00000474437.1	n.536C>G		non_coding_transcript_exon_variant	4/4	3
BAZ2B	ENST00000548440.1	n.510C>G		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 20 AN: 151564 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000921

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000884

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000904 AC: 21 AN: 232280 Hom.: 0 AF XY: 0.0000556 AC XY: 7 AN XY: 125964

Gnomad AFR exome AF: 0.0000668

Gnomad AMR exome AF: 0.000537

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000485 AC: 70 AN: 1444268 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 29 AN XY: 717754

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000598

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000379

Gnomad4 OTH exome AF: 0.0000670

GnomAD4 genome AF: 0.000132 AC: 20 AN: 151680 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74110

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000920

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000884

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.000178

ESP6500AA AF: 0.000275 AC: 1

ESP6500EA AF: 0.000123 AC: 1

ExAC AF: 0.0000580 AC: 7

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	19
Dann	Benign	0.77
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.0092	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.87	N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.62	N;N
REVEL	Benign	0.074
Sift	Benign	1.0	T;T
Sift4G	Benign	0.91	T;T
Polyphen		0.0	B;B
Vest4		0.081
MutPred		0.24		.;Loss of loop (P = 0.0374);
MVP		0.12
MPC		0.036
ClinPred		0.023	T
GERP RS		1.6
Varity_R		0.035
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs200299773; hg19: chr2-160182377;