BRWD1 p.Ser784Ser

Variant names:

• chr21-39247829-C-C
• NM_033656.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr21-39247830--
• chr21-39247830-C-A
• chr21-39247830-C-G
• chr21-39247830-C-T
• chr21-39247830-CGA-ACT
• chr21-39247830-CGA-GCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033656.4(BRWD1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRWD1 NM_033656.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744
• Publications: 0 publications found

Genes affected

BRWD1 (HGNC:12760): (bromodomain and WD repeat domain containing 1) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) residues which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 2 bromodomains and multiple WD repeats. This gene is located within the Down syndrome region-2 on chromosome 21. Alternative splicing of this gene generates multiple transcript variants encoding distinct isoforms. In mouse, this gene encodes a nuclear protein that has a polyglutamine-containing region that functions as a transcriptional activation domain which may regulate chromatin remodelling and associates with a component of the SWI/SNF chromatin remodelling complex.[provided by RefSeq, Jun 2011]

BRWD1 Gene-Disease associations (from GenCC):

• agammaglobulinemia

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• ciliary dyskinesia, primary, 51

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000297893 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033656.4. 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
	BRWD1	NM_033656.4	MANE Select	c.		exon_region	Exon 21 of 41	NP_387505.1	Q9NSI6-2
	BRWD1	NM_018963.5		c.		exon_region	Exon 21 of 42	NP_061836.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRWD1	ENST00000342449.8	TSL:1 MANE Select	c.		exon_region	Exon 21 of 41	ENSP00000344333.3	Q9NSI6-2
	BRWD1	ENST00000333229.6	TSL:1	c.		exon_region	Exon 21 of 42	ENSP00000330753.2	Q9NSI6-1
	BRWD1	ENST00000380800.7	TSL:1	c.		exon_region	Exon 21 of 42	ENSP00000370178.3	Q9NSI6-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.74

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-40619755;