8-66896253-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_173518.5(MCMDC2):c.1363C>T(p.Gln455*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000248 in 1,611,922 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
MCMDC2
NM_173518.5 stop_gained
NM_173518.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 3.99
Genes affected
MCMDC2 (HGNC:26368): (minichromosome maintenance domain containing 2) Predicted to enable ATP binding activity and DNA binding activity. Predicted to be involved in double-strand break repair via break-induced replication. Predicted to act upstream of or within gamete generation and meiosis I cell cycle process. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-66896253-C-T is Pathogenic according to our data. Variant chr8-66896253-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2690955.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249124Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134676
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459764Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726118
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74334
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Male infertility with azoospermia or oligozoospermia due to single gene mutation Pathogenic:1
Sep 01, 2023
Laan Lab, Human Genetics Research Group, University of Tartu
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: research
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Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
Vest4
ClinPred
D
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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