rs138097363

Variant names:

• chr6-32974609-C-A
• rs138097363
• NM_005104.4:c.177C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32974609-C-A
• chr6-32974609-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4 BP6_Moderate BP7 BS2

The NM_005104.4(BRD2):​c.177C>A​(p.Ala59Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,614,228 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (29 hom.)
• Consequence: BRD2 NM_005104.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.331
• Publications: 7 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.261).
• BP6: Variant 6-32974609-C-A is Benign according to our data. Variant chr6-32974609-C-A is described in ClinVar as [Benign]. Clinvar id is 720050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.331 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 29 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD2	NM_005104.4	c.177C>A	p.Ala59Ala	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.177C>A	p.Ala59Ala	synonymous_variant	Exon 3 of 13	1	NM_005104.4	ENSP00000363958.4

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 418 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00868

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00341

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.00387 AC: 974 AN: 251488 AF XY: 0.00466

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00675

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00386

Gnomad OTH exome AF: 0.00749

GnomAD4 exome AF: 0.00313 AC: 4573 AN: 1461892 Hom.: 29 Cov.: 33 AF XY: 0.00338 AC XY: 2455 AN XY: 727248

African (AFR) AF: 0.00200 AC: 67 AN: 33480

American (AMR) AF: 0.00360 AC: 161 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00746 AC: 195 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00951 AC: 820 AN: 86258

European-Finnish (FIN) AF: 0.000318 AC: 17 AN: 53420

Middle Eastern (MID) AF: 0.0151 AC: 87 AN: 5768

European-Non Finnish (NFE) AF: 0.00268 AC: 2985 AN: 1112010

Other (OTH) AF: 0.00391 AC: 236 AN: 60396

GnomAD4 genome AF: 0.00274 AC: 418 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.00293 AC XY: 218 AN XY: 74508

African (AFR) AF: 0.000891 AC: 37 AN: 41548

American (AMR) AF: 0.00444 AC: 68 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.00869 AC: 42 AN: 4832

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00341 AC: 232 AN: 68038

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00367 Hom.: 15

Bravo AF: 0.00307

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00545

EpiControl AF: 0.00545

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		-0.33
Mutation Taster		=288/12	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: rs138097363; hg19: chr6-32942386; COSMIC: COSV100875907; COSMIC: COSV100875907;