chr8-6499875-T-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_024596.5(MCPH1):c.2160T>A(p.Gly720=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
MCPH1
NM_024596.5 synonymous
NM_024596.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.158
Genes affected
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 8-6499875-T-A is Benign according to our data. Variant chr8-6499875-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2957761.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.158 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCPH1 | NM_024596.5 | c.2160T>A | p.Gly720= | synonymous_variant | 12/14 | ENST00000344683.10 | |
ANGPT2 | NM_001118887.2 | c.*3226A>T | 3_prime_UTR_variant | 9/9 | ENST00000629816.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCPH1 | ENST00000344683.10 | c.2160T>A | p.Gly720= | synonymous_variant | 12/14 | 1 | NM_024596.5 | P1 | |
ANGPT2 | ENST00000629816.3 | c.*3226A>T | 3_prime_UTR_variant | 9/9 | 1 | NM_001118887.2 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249572Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135404
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461118Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726880
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GnomAD4 genome Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at