rs1982386
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The ENST00000344683.10(MCPH1):c.2214+14026C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,052,964 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0026 ( 8 hom. )
Consequence
MCPH1
ENST00000344683.10 intron
ENST00000344683.10 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.00600
Genes affected
ANGPT2 (HGNC:485): (angiopoietin 2) This gene belongs to the angiopoietin family of growth factors. The protein encoded by this gene is an antagonist of angiopoietin 1, and both angiopoietin 1 and angiopoietin 2 are ligands for the endothelial TEK receptor tyrosine kinase. Angiopoietin 2 is upregulated in multiple inflammatory diseases and is implicated in the direct control of inflammation-related signaling pathways. The encoded protein affects angiogenesis during embryogenesis and tumorigenesis, disrupts the vascular remodeling ability of angiopoietin 1, and may induce endothelial cell apoptosis. This gene serves a prognostic biomarker for acute respiratory distress syndrome. [provided by RefSeq, Aug 2020]
MCPH1 (HGNC:6954): (microcephalin 1) This gene encodes a DNA damage response protein. The encoded protein may play a role in G2/M checkpoint arrest via maintenance of inhibitory phosphorylation of cyclin-dependent kinase 1. Mutations in this gene have been associated with primary autosomal recessive microcephaly 1 and premature chromosome condensation syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00174 (264/152156) while in subpopulation NFE AF= 0.00316 (215/67984). AF 95% confidence interval is 0.00282. There are 0 homozygotes in gnomad4. There are 111 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANGPT2 | NM_001118887.2 | c.1030-111G>C | intron_variant | ENST00000629816.3 | NP_001112359.1 | |||
MCPH1 | NM_024596.5 | c.2214+14026C>G | intron_variant | ENST00000344683.10 | NP_078872.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MCPH1 | ENST00000344683.10 | c.2214+14026C>G | intron_variant | 1 | NM_024596.5 | ENSP00000342924 | P1 | |||
ANGPT2 | ENST00000629816.3 | c.1030-111G>C | intron_variant | 1 | NM_001118887.2 | ENSP00000486858 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00174 AC: 264AN: 152038Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00263 AC: 2373AN: 900808Hom.: 8 AF XY: 0.00259 AC XY: 1168AN XY: 451558
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GnomAD4 genome AF: 0.00174 AC: 264AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.00149 AC XY: 111AN XY: 74384
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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