chr11-65020495-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000246747.9(ARL2):c.416G>A(p.Arg139His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000615 in 1,608,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R139R) has been classified as Likely benign.
Frequency
Consequence
ENST00000246747.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARL2 | NM_001667.4 | c.416G>A | p.Arg139His | missense_variant | 4/5 | ENST00000246747.9 | NP_001658.2 | |
ARL2-SNX15 | NR_037650.2 | n.387+1762G>A | intron_variant, non_coding_transcript_variant | |||||
ARL2 | NM_001199745.2 | c.340-1226G>A | intron_variant | NP_001186674.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARL2 | ENST00000246747.9 | c.416G>A | p.Arg139His | missense_variant | 4/5 | 1 | NM_001667.4 | ENSP00000246747 | P1 | |
ARL2 | ENST00000529384.5 | c.416G>A | p.Arg139His | missense_variant | 4/6 | 3 | ENSP00000436021 | P1 | ||
ARL2 | ENST00000533729.1 | c.340-1226G>A | intron_variant | 5 | ENSP00000432971 | |||||
ARL2 | ENST00000531533.1 | n.229G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000207 AC: 5AN: 241628Hom.: 0 AF XY: 0.0000383 AC XY: 5AN XY: 130676
GnomAD4 exome AF: 0.0000652 AC: 95AN: 1456794Hom.: 0 Cov.: 32 AF XY: 0.0000635 AC XY: 46AN XY: 724290
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74340
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2022 | The c.416G>A (p.R139H) alteration is located in exon 4 (coding exon 4) of the ARL2 gene. This alteration results from a G to A substitution at nucleotide position 416, causing the arginine (R) at amino acid position 139 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at