2-96115238-CTCCTCCTCT-C

Variant names:

• chr2-96115238-CTCCTCCTCT-C
• rs4066772
• NM_000682.7:c.903_911delAGAGGAGGA

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_000682.7(ADRA2B):​c.903_911delAGAGGAGGA​(p.Glu302_Glu304del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,557,570 control chromosomes in the GnomAD database, including 81,834 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6816 hom., cov: 20)
  • Exomes 𝑓: 0.32 (75018 hom.)
• Consequence: ADRA2B NM_000682.7 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.02
• Publications: 3 publications found

Genes affected

ADRA2B (HGNC:282): (adrenoceptor alpha 2B) This intronless gene encodes a seven-pass transmembrane protein. This protein is a member of a subfamily of G protein-coupled receptors that regulate neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. [provided by RefSeq, Apr 2014]

ADRA2B Gene-Disease associations (from GenCC):

• benign adult familial myoclonic epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P
• epilepsy, familial adult myoclonic, 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_000682.7
• BP6: Variant 2-96115238-CTCCTCCTCT-C is Benign according to our data. Variant chr2-96115238-CTCCTCCTCT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 767169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000682.7. 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
	ADRA2B	NM_000682.7	MANE Select	c.903_911delAGAGGAGGA	p.Glu302_Glu304del	disruptive_inframe_deletion	Exon 1 of 1	NP_000673.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA2B	ENST00000620793.2	TSL:6 MANE Select	c.903_911delAGAGGAGGA	p.Glu302_Glu304del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000480573.1	P18089

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43000 AN: 151702 Hom.: 6808 Cov.: 20

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.322 AC: 453186 AN: 1405750 Hom.: 75018 AF XY: 0.318 AC XY: 220878 AN XY: 694002

African (AFR) AF: 0.142 AC: 4542 AN: 31894

American (AMR) AF: 0.327 AC: 11922 AN: 36418

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 4997 AN: 24970

East Asian (EAS) AF: 0.394 AC: 14343 AN: 36402

South Asian (SAS) AF: 0.223 AC: 17960 AN: 80508

European-Finnish (FIN) AF: 0.456 AC: 22622 AN: 49580

Middle Eastern (MID) AF: 0.146 AC: 830 AN: 5694

European-Non Finnish (NFE) AF: 0.332 AC: 359155 AN: 1081936

Other (OTH) AF: 0.288 AC: 16815 AN: 58348

GnomAD4 genome AF: 0.283 AC: 43041 AN: 151820 Hom.: 6816 Cov.: 20 AF XY: 0.288 AC XY: 21392 AN XY: 74210

African (AFR) AF: 0.158 AC: 6540 AN: 41500

American (AMR) AF: 0.293 AC: 4474 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3472

East Asian (EAS) AF: 0.423 AC: 2163 AN: 5108

South Asian (SAS) AF: 0.219 AC: 1054 AN: 4808

European-Finnish (FIN) AF: 0.462 AC: 4877 AN: 10552

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22281 AN: 67814

Other (OTH) AF: 0.250 AC: 529 AN: 2112

Alfa AF: 0.0144 Hom.: 2779

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

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

Other links and lift over

dbSNP: rs4066772; hg19: chr2-96780986; COSMIC: COSV108249057;