10-111078792-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting
The NM_000681.4(ADRA2A):āc.796A>Gā(p.Asn266Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,382,858 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N266K) has been classified as Likely benign.
Frequency
Consequence
NM_000681.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADRA2A | NM_000681.4 | c.796A>G | p.Asn266Asp | missense_variant | 1/1 | ENST00000280155.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADRA2A | ENST00000280155.4 | c.796A>G | p.Asn266Asp | missense_variant | 1/1 | NM_000681.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000173 AC: 26AN: 150326Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000899 AC: 2AN: 22236Hom.: 0 AF XY: 0.0000862 AC XY: 1AN XY: 11598
GnomAD4 exome AF: 0.000114 AC: 141AN: 1232422Hom.: 4 Cov.: 31 AF XY: 0.000175 AC XY: 105AN XY: 598884
GnomAD4 genome AF: 0.000173 AC: 26AN: 150436Hom.: 0 Cov.: 33 AF XY: 0.000204 AC XY: 15AN XY: 73524
ClinVar
Submissions by phenotype
ADRA2A-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 18, 2023 | The ADRA2A c.796A>G variant is predicted to result in the amino acid substitution p.Asn266Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.23% of alleles in individuals of South Asian descent (2 of 856 alleles), although it is less common in or absent from other populations in gnomAD (http://gnomad.broadinstitute.org/variant/10-112838550-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at