chr3-127599437-T-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004526.4(MCM2):c.126T>C(p.Pro42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,614,134 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 33 hom. )
Consequence
MCM2
NM_004526.4 synonymous
NM_004526.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.09
Genes affected
MCM2 (HGNC:6944): (minichromosome maintenance complex component 2) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein forms a complex with MCM4, 6, and 7, and has been shown to regulate the helicase activity of the complex. This protein is phosphorylated, and thus regulated by, protein kinases CDC2 and CDC7. Multiple alternatively spliced transcript variants have been found, but the full-length nature of some variants has not been defined. [provided by RefSeq, Oct 2012]
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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=-0.63).
BP6
?
Variant 3-127599437-T-C is Benign according to our data. Variant chr3-127599437-T-C is described in ClinVar as [Benign]. Clinvar id is 1254967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.09 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00107 (163/152274) while in subpopulation SAS AF= 0.0218 (105/4822). AF 95% confidence interval is 0.0184. There are 4 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 164 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCM2 | NM_004526.4 | c.126T>C | p.Pro42= | synonymous_variant | 2/16 | ENST00000265056.12 | |
MCM2 | XM_024453531.2 | c.99T>C | p.Pro33= | synonymous_variant | 2/16 | ||
MCM2 | NR_073375.2 | n.182T>C | non_coding_transcript_exon_variant | 2/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCM2 | ENST00000265056.12 | c.126T>C | p.Pro42= | synonymous_variant | 2/16 | 1 | NM_004526.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00108 AC: 164AN: 152156Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.00257 AC: 645AN: 251420Hom.: 17 AF XY: 0.00347 AC XY: 471AN XY: 135906
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GnomAD4 exome AF: 0.00121 AC: 1766AN: 1461860Hom.: 33 Cov.: 30 AF XY: 0.00172 AC XY: 1253AN XY: 727226
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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