rs199880428
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000393.5(COL5A2):c.961-14T>C 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 0.000239 in 1,605,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
COL5A2
NM_000393.5 splice_polypyrimidine_tract, intron
NM_000393.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.57
Genes affected
COL5A2 (HGNC:2210): (collagen type V alpha 2 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 2-189079121-A-G is Benign according to our data. Variant chr2-189079121-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 256007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.961-14T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000374866.9 | |||
COL5A2 | XM_011510573.4 | c.823-14T>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
COL5A2 | XM_047443251.1 | c.823-14T>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
COL5A2 | XM_047443252.1 | c.823-14T>C | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.961-14T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000393.5 | P1 | |||
COL5A2 | ENST00000618828.1 | c.331-14T>C | splice_polypyrimidine_tract_variant, intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152198Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000108 AC: 27AN: 250726Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135514
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GnomAD4 exome AF: 0.000248 AC: 361AN: 1453036Hom.: 0 Cov.: 28 AF XY: 0.000216 AC XY: 156AN XY: 723484
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GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74344
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at