chr6-32974487-T-C

Variant names:

• chr6-32974487-T-C
• rs3752528
• NM_005104.4:c.55T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005104.4(BRD2):​c.55T>C​(p.Leu19Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000496 in 1,612,478 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (4 hom.)
• Consequence: BRD2 NM_005104.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.243
• Publications: 1 publications found

Genes affected

BRD2 (HGNC:1103): (bromodomain containing 2) This gene encodes a transcriptional regulator that belongs to the BET (bromodomains and extra terminal domain) family of proteins. This protein associates with transcription complexes and with acetylated chromatin during mitosis, and it selectively binds to the acetylated lysine-12 residue of histone H4 via its two bromodomains. The gene maps to the major histocompatability complex (MHC) class II region on chromosome 6p21.3, but sequence comparison suggests that the protein is not involved in the immune response. This gene has been implicated in juvenile myoclonic epilepsy, a common form of epilepsy that becomes apparent in adolescence. Multiple alternatively spliced variants have been described for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 6-32974487-T-C is Benign according to our data. Variant chr6-32974487-T-C is described in ClinVar as [Benign]. Clinvar id is 726131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.243 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD2	NM_005104.4	c.55T>C	p.Leu19Leu	synonymous_variant	Exon 3 of 13	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.55T>C	p.Leu19Leu	synonymous_variant	Exon 3 of 13	1	NM_005104.4	ENSP00000363958.4

Frequencies

GnomAD3 genomes AF: 0.000552 AC: 84 AN: 152188 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000967 AC: 242 AN: 250240 AF XY: 0.000886

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00973

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000490 AC: 716 AN: 1460172 Hom.: 4 Cov.: 30 AF XY: 0.000463 AC XY: 336 AN XY: 726024

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.000448 AC: 20 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.0137 AC: 544 AN: 39644

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86244

European-Finnish (FIN) AF: 0.000955 AC: 51 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1110548

Other (OTH) AF: 0.000497 AC: 30 AN: 60336

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152306 Hom.: 1 Cov.: 32 AF XY: 0.000698 AC XY: 52 AN XY: 74482

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.000457 AC: 7 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5180

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68014

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000615 Hom.: 1

Bravo AF: 0.000642

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

BRD2-related disorder Benign:1

Jun 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.24
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=300/0	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: rs3752528; hg19: chr6-32942264; COSMIC: COSV100875886; COSMIC: COSV100875886;