chr2-159325889-T-G

Position:

• chr2-159325889-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013450.4(BAZ2B):​c.5973A>C​(p.Lys1991Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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)
• Consequence: BAZ2B NM_013450.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.851

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAZ2B	NM_013450.4	c.5973A>C	p.Lys1991Asn	missense_variant	35/37	ENST00000392783.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAZ2B	ENST00000392783.7	c.5973A>C	p.Lys1991Asn	missense_variant	35/37	5	NM_013450.4	P1
BAZ2B	ENST00000392782.5	c.5865A>C	p.Lys1955Asn	missense_variant	34/36	1
BAZ2B	ENST00000474437.1	n.513A>C		non_coding_transcript_exon_variant	4/4	3
BAZ2B	ENST00000548440.1	n.487A>C		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2023

The c.5973A>C (p.K1991N) alteration is located in exon 35 (coding exon 33) of the BAZ2B gene. This alteration results from a A to C substitution at nucleotide position 5973, causing the lysine (K) at amino acid position 1991 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.019	.;T
Eigen	Benign	0.0054
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	.;M
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.028	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.66
MutPred		0.45		.;Loss of methylation at K1991 (P = 0.0123);
MVP		0.18
MPC		0.27
ClinPred		0.78	D
GERP RS		3.2
Varity_R		0.14
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-160182400;