rs41316929
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000089.4(COL1A2):c.1036-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00952 in 1,613,322 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0059 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0099 ( 89 hom. )
Consequence
COL1A2
NM_000089.4 intron
NM_000089.4 intron
Scores
2
Splicing: ADA: 0.00001305
2
Clinical Significance
Conservation
PhyloP100: -1.20
Genes affected
COL1A2 (HGNC:2198): (collagen type I alpha 2 chain) This gene encodes the pro-alpha2 chain of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIB, recessive Ehlers-Danlos syndrome Classical type, idiopathic osteoporosis, and atypical Marfan syndrome. Symptoms associated with mutations in this gene, however, tend to be less severe than mutations in the gene for the alpha1 chain of type I collagen (COL1A1) reflecting the different role of alpha2 chains in matrix integrity. Three transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 7-94410230-A-G is Benign according to our data. Variant chr7-94410230-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 360951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00593 (903/152288) while in subpopulation NFE AF= 0.0104 (708/68008). AF 95% confidence interval is 0.00978. There are 4 homozygotes in gnomad4. There are 419 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AD,AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| COL1A2 | NM_000089.4 | c.1036-12A>G | intron_variant | ENST00000297268.11 | NP_000080.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| COL1A2 | ENST00000297268.11 | c.1036-12A>G | intron_variant | 1 | NM_000089.4 | ENSP00000297268.6 |
Frequencies
GnomAD3 genomes 0.00593 AC: 902AN: 152170Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00554 AC: 1392AN: 251346Hom.: 6 AF XY: 0.00561 AC XY: 762AN XY: 135858
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GnomAD4 exome AF: 0.00989 AC: 14452AN: 1461034Hom.: 89 Cov.: 32 AF XY: 0.00953 AC XY: 6929AN XY: 726848
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GnomAD4 genome 0.00593 AC: 903AN: 152288Hom.: 4 Cov.: 32 AF XY: 0.00563 AC XY: 419AN XY: 74458
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
| Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 21, 2017 | - - |
| Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 08, 2023 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | COL1A2: BS2 - |
Osteogenesis imperfecta 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. - |
not specified Benign:1
| Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 20, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Ehlers-danlos syndrome, arthrochalasia type, 2 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. - |
Osteogenesis imperfecta type I;C0268335:Ehlers-Danlos syndrome, classic type, 1 Benign:1
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at