5-138152723-T-A

Position:

• chr5-138152723-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139199.2(BRD8):​c.2615A>T​(p.Asp872Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRD8 NM_139199.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

Genes affected

BRD8 (HGNC:19874): (bromodomain containing 8) The protein encoded by this gene interacts with thyroid hormone receptor in a ligand-dependent manner and enhances thyroid hormone-dependent activation from thyroid response elements. This protein contains a bromodomain and is thought to be a nuclear receptor coactivator. Multiple alternatively spliced transcript variants that encode distinct isoforms have been identified. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14655128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD8	NM_139199.2	c.2615A>T	p.Asp872Val	missense_variant	21/27	ENST00000254900.10	NP_631938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRD8	ENST00000254900.10	c.2615A>T	p.Asp872Val	missense_variant	21/27	1	NM_139199.2	ENSP00000254900.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2024

The c.2615A>T (p.D872V) alteration is located in exon 21 (coding exon 21) of the BRD8 gene. This alteration results from a A to T substitution at nucleotide position 2615, causing the aspartic acid (D) at amino acid position 872 to be replaced by a valine (V). 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	Benign	0.089
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.071
Eigen_PC	Benign	0.021
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.22	T
Polyphen		0.84	P
Vest4		0.21
MutPred		0.36		Loss of disorder (P = 0.0352);
MVP		0.40
MPC		0.34
ClinPred		0.88	D
GERP RS		4.2
Varity_R		0.14
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-137488412;