2-127420008-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000312.4(PROC):āc.66T>Cā(p.Pro22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000625 in 1,613,240 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0013 ( 7 hom., cov: 33)
Exomes š: 0.00056 ( 15 hom. )
Consequence
PROC
NM_000312.4 synonymous
NM_000312.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.31
Genes affected
PROC (HGNC:9451): (protein C, inactivator of coagulation factors Va and VIIIa) This gene encodes a vitamin K-dependent plasma glycoprotein. The encoded protein is cleaved to its activated form by the thrombin-thrombomodulin complex. This activated form contains a serine protease domain and functions in degradation of the activated forms of coagulation factors V and VIII. Mutations in this gene have been associated with thrombophilia due to protein C deficiency, neonatal purpura fulminans, and recurrent venous thrombosis.[provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 2-127420008-T-C is Benign according to our data. Variant chr2-127420008-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 331102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.31 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00127 (193/152220) while in subpopulation EAS AF= 0.0273 (141/5166). AF 95% confidence interval is 0.0236. There are 7 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROC | NM_000312.4 | c.66T>C | p.Pro22= | synonymous_variant | 2/9 | ENST00000234071.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROC | ENST00000234071.8 | c.66T>C | p.Pro22= | synonymous_variant | 2/9 | 1 | NM_000312.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00128 AC: 194AN: 152102Hom.: 7 Cov.: 33
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GnomAD3 exomes AF: 0.00213 AC: 536AN: 251228Hom.: 11 AF XY: 0.00194 AC XY: 263AN XY: 135854
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GnomAD4 exome AF: 0.000559 AC: 816AN: 1461020Hom.: 15 Cov.: 34 AF XY: 0.000532 AC XY: 387AN XY: 726820
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GnomAD4 genome AF: 0.00127 AC: 193AN: 152220Hom.: 7 Cov.: 33 AF XY: 0.00140 AC XY: 104AN XY: 74422
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Thrombophilia due to protein C deficiency, autosomal dominant Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 20, 2024 | - - |
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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