chr10-122456894-A-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001099667.3(ARMS2):c.298-13A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,510,222 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.012 ( 29 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 62 hom. )
Consequence
ARMS2
NM_001099667.3 splice_polypyrimidine_tract, intron
NM_001099667.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.213
Genes affected
ARMS2 (HGNC:32685): (age-related maculopathy susceptibility 2) This gene encodes a small secreted protein specific to primates. This protein is a component of the choroidal extracellular matrix of the eye. Mutations in this gene are associated with age-related macular degeneration. [provided by RefSeq, Sep 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 10-122456894-A-T is Benign according to our data. Variant chr10-122456894-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 299032.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1804/151196) while in subpopulation AFR AF= 0.04 (1647/41158). AF 95% confidence interval is 0.0384. There are 29 homozygotes in gnomad4. There are 850 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 29 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARMS2 | NM_001099667.3 | c.298-13A>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000528446.1 | |||
LOC105378525 | XR_946382.3 | n.1874+1601T>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARMS2 | ENST00000528446.1 | c.298-13A>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001099667.3 | P1 | |||
ENST00000650300.1 | n.1852+1601T>A | intron_variant, non_coding_transcript_variant | |||||||
ENST00000647969.1 | n.182+1601T>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0119 AC: 1798AN: 151076Hom.: 29 Cov.: 32
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GnomAD3 exomes AF: 0.00386 AC: 538AN: 139318Hom.: 11 AF XY: 0.00398 AC XY: 294AN XY: 73790
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GnomAD4 exome AF: 0.00199 AC: 2708AN: 1359026Hom.: 62 Cov.: 33 AF XY: 0.00211 AC XY: 1417AN XY: 670354
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Age related macular degeneration 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Macular degeneration Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at