chr2-127419983-G-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000312.4(PROC):c.41G>A(p.Trp14*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000312.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461464Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727048
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Reduced protein C activity Pathogenic:1
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Thrombophilia due to protein C deficiency, autosomal dominant Pathogenic:1
This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp14*) in the PROC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PROC are known to be pathogenic (PMID: 17152060). This premature translational stop signal has been observed in individual(s) with protein C deficiency (PMID: 8462980). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 972257). This variant is also known as Trp-29->term. -
not provided Pathogenic:1
PM2, PVS1 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at