chr8-6499686-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001118887.2(ANGPT2):c.*3415T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 627,316 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.013 ( 24 hom., cov: 33)
Exomes 𝑓: 0.016 ( 70 hom. )
Consequence
ANGPT2
NM_001118887.2 3_prime_UTR
NM_001118887.2 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0430
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 8-6499686-A-G is Benign according to our data. Variant chr8-6499686-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1187061.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0131 (1995/152326) while in subpopulation NFE AF= 0.019 (1291/68024). AF 95% confidence interval is 0.0181. There are 24 homozygotes in gnomad4. There are 945 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1994 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANGPT2 | NM_001118887.2 | c.*3415T>C | 3_prime_UTR_variant | 9/9 | ENST00000629816.3 | ||
MCPH1 | NM_024596.5 | c.2137-166A>G | intron_variant | ENST00000344683.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANGPT2 | ENST00000629816.3 | c.*3415T>C | 3_prime_UTR_variant | 9/9 | 1 | NM_001118887.2 | P4 | ||
MCPH1 | ENST00000344683.10 | c.2137-166A>G | intron_variant | 1 | NM_024596.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0131 AC: 1994AN: 152208Hom.: 24 Cov.: 33
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GnomAD4 exome AF: 0.0156 AC: 7407AN: 474990Hom.: 70 Cov.: 5 AF XY: 0.0148 AC XY: 3735AN XY: 252628
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GnomAD4 genome ? AF: 0.0131 AC: 1995AN: 152326Hom.: 24 Cov.: 33 AF XY: 0.0127 AC XY: 945AN XY: 74484
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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 | GeneDx | Jul 15, 2018 | - - |
Computational scores
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Name
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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