chr2-159324908-G-T

Variant names:

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

Variant summary

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

The NM_013450.4(BAZ2B):​c.6256C>A​(p.Leu2086Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: BAZ2B NM_013450.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97

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 rank	MANE	Protein	UniProt
BAZ2B	NM_013450.4	c.6256C>A	p.Leu2086Ile	missense_variant	Exon 36 of 37	ENST00000392783.7	NP_038478.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAZ2B	ENST00000392783.7	c.6256C>A	p.Leu2086Ile	missense_variant	Exon 36 of 37	5	NM_013450.4	ENSP00000376534.2
BAZ2B	ENST00000392782.5	c.6148C>A	p.Leu2050Ile	missense_variant	Exon 35 of 36	1		ENSP00000376533.1
BAZ2B	ENST00000548440.1	n.770C>A		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000497 AC: 1 AN: 201134 Hom.: 0 AF XY: 0.00000905 AC XY: 1 AN XY: 110524

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000102

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1409464 Hom.: 0 Cov.: 28 AF XY: 0.00000143 AC XY: 1 AN XY: 700160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.15e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.067	.;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.0	.;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;D
Vest4		0.54
MutPred		0.67		.;Gain of catalytic residue at L2091 (P = 0.0213);
MVP		0.27
MPC		0.29
ClinPred		0.70	D
GERP RS		5.5
Varity_R		0.42
gMVP		0.28

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: rs1226362424; hg19: chr2-160181419;