NM_004370.6:c.2314C>T
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_004370.6(COL12A1):c.2314C>T(p.Pro772Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004370.6 missense
Scores
Clinical Significance
Conservation
Publications
- Bethlem myopathy 2Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
- Bethlem myopathy 2Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Illumina, Genomics England PanelApp
- Ullrich congenital muscular dystrophy 2Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Bethlem myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Ullrich congenital muscular dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152104Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000281 AC: 7AN: 249392 AF XY: 0.0000370 show subpopulations
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461856Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727228 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74314 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: COL12A1 c.2314C>T (p.Pro772Ser) results in a non-conservative amino acid change located in a fibronectin type III repeat (IPR003961) in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 280790 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2314C>T in individuals affected with Bethlem myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Inborn genetic diseases Uncertain:1
The c.2314C>T (p.P772S) alteration is located in exon 12 (coding exon 11) of the COL12A1 gene. This alteration results from a C to T substitution at nucleotide position 2314, causing the proline (P) at amino acid position 772 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at