rs879255577

Positions:

• chr2-96115463-CAAAGCCCCACCA-CCTGCCAAAC

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PS1 PM2 PM4_Supporting

The NM_000682.7(ADRA2B):​c.675_686delTGGTGGGGCTTTinsGTTTGGCAG​(p.His225_Leu229delinsGlnPheGlyArg) variant causes a missense, conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in Lovd.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADRA2B NM_000682.7 missense, conservative_inframe_deletion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.76

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PS1: Transcript NM_000682.7 (ADRA2B) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000682.7. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA2B	NM_000682.7	c.675_686delTGGTGGGGCTTTinsGTTTGGCAG	p.His225_Leu229delinsGlnPheGlyArg	missense_variant, conservative_inframe_deletion		ENST00000620793.2	NP_000673.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA2B	ENST00000620793.2	c.675_686delTGGTGGGGCTTTinsGTTTGGCAG	p.His225_Leu229delinsGlnPheGlyArg	missense_variant, conservative_inframe_deletion		6	NM_000682.7	ENSP00000480573.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Epilepsy, familial adult myoclonic, 2 Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jan 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs879255577; hg19: chr2-96781203;