NM_013450.4:c.6246A>G

Variant names:

• chr2-159324918-T-C
• rs371273841
• NM_013450.4:c.6246A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_013450.4(BAZ2B):​c.6246A>G​(p.Ala2082Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000772 in 1,554,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: BAZ2B NM_013450.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.312
• Publications: 3 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 2-159324918-T-C is Benign according to our data. Variant chr2-159324918-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 715906.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.312 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00036 (54/149962) while in subpopulation AFR AF = 0.00111 (45/40582). AF 95% confidence interval is 0.000851. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High AC in GnomAd4 at 54 AD gene.

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.6246A>G	p.Ala2082Ala	synonymous	Exon 36 of 37	NP_038478.2	Q9UIF8-1
	BAZ2B	NM_001329857.2		c.6189A>G	p.Ala2063Ala	synonymous	Exon 36 of 37	NP_001316786.1
	BAZ2B	NM_001329858.2		c.6171A>G	p.Ala2057Ala	synonymous	Exon 36 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.6246A>G	p.Ala2082Ala	synonymous	Exon 36 of 37	ENSP00000376534.2	Q9UIF8-1
	BAZ2B	ENST00000392782.5	TSL:1	c.6138A>G	p.Ala2046Ala	synonymous	Exon 35 of 36	ENSP00000376533.1	Q9UIF8-5
	BAZ2B	ENST00000911534.1		c.6246A>G	p.Ala2082Ala	synonymous	Exon 37 of 38	ENSP00000581593.1

Frequencies

GnomAD3 genomes AF: 0.000360 AC: 54 AN: 149848 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000535

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: 0.00

Gnomad OTH AF: 0.000491

GnomAD2 exomes AF: 0.0000848 AC: 17 AN: 200362 AF XY: 0.0000726

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.0000458

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000102

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.0000470 AC: 66 AN: 1404756 Hom.: 0 Cov.: 28 AF XY: 0.0000444 AC XY: 31 AN XY: 697536

African (AFR) AF: 0.00105 AC: 31 AN: 29526

American (AMR) AF: 0.000157 AC: 5 AN: 31834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24942

East Asian (EAS) AF: 0.00 AC: 0 AN: 35294

South Asian (SAS) AF: 0.00 AC: 0 AN: 74906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52944

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5646

European-Non Finnish (NFE) AF: 0.00000733 AC: 8 AN: 1091596

Other (OTH) AF: 0.000362 AC: 21 AN: 58068

GnomAD4 genome AF: 0.000360 AC: 54 AN: 149962 Hom.: 0 Cov.: 24 AF XY: 0.000369 AC XY: 27 AN XY: 73164

African (AFR) AF: 0.00111 AC: 45 AN: 40582

American (AMR) AF: 0.000535 AC: 8 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67676

Other (OTH) AF: 0.000486 AC: 1 AN: 2058

Alfa AF: 0.000305 Hom.: 0

Bravo AF: 0.000586

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.7
DANN	Benign	0.69
PhyloP100		-0.31
Mutation Taster		=96/4	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: rs371273841; hg19: chr2-160181429;