X-55009268-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000032.5(ALAS2):c.1676G>A(p.Arg559His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,203,790 control chromosomes in the GnomAD database, including 5 homozygotes. There are 932 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000032.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALAS2 | NM_000032.5 | c.1676G>A | p.Arg559His | missense_variant | Exon 11 of 11 | ENST00000650242.1 | NP_000023.2 | |
ALAS2 | NM_001037968.4 | c.1637G>A | p.Arg546His | missense_variant | Exon 11 of 11 | NP_001033057.1 | ||
ALAS2 | NM_001037967.4 | c.1565G>A | p.Arg522His | missense_variant | Exon 10 of 10 | NP_001033056.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALAS2 | ENST00000650242.1 | c.1676G>A | p.Arg559His | missense_variant | Exon 11 of 11 | NM_000032.5 | ENSP00000497236.1 | |||
ALAS2 | ENST00000396198.7 | c.1637G>A | p.Arg546His | missense_variant | Exon 11 of 11 | 5 | ENSP00000379501.3 | |||
ALAS2 | ENST00000335854.8 | c.1565G>A | p.Arg522His | missense_variant | Exon 10 of 10 | 2 | ENSP00000337131.4 | |||
ALAS2 | ENST00000498636.1 | c.802G>A | p.Ala268Thr | missense_variant | Exon 5 of 5 | 3 | ENSP00000495662.1 |
Frequencies
GnomAD3 genomes AF: 0.00161 AC: 178AN: 110760Hom.: 1 Cov.: 23 AF XY: 0.00155 AC XY: 51AN XY: 32962
GnomAD3 exomes AF: 0.00227 AC: 381AN: 167537Hom.: 3 AF XY: 0.00190 AC XY: 105AN XY: 55189
GnomAD4 exome AF: 0.00257 AC: 2813AN: 1092980Hom.: 4 Cov.: 31 AF XY: 0.00245 AC XY: 881AN XY: 359068
GnomAD4 genome AF: 0.00161 AC: 178AN: 110810Hom.: 1 Cov.: 23 AF XY: 0.00154 AC XY: 51AN XY: 33022
ClinVar
Submissions by phenotype
not provided Benign:4
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This variant is associated with the following publications: (PMID: 26562225, 21653323, 22995991, 15678587, 22740690, 30678654, 22269113, 20848343, 15678585, 16121195) -
not specified Benign:1
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ALAS2-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
X-linked sideroblastic anemia 1 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at