chr8-6499714-A-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001118887.2(ANGPT2):c.*3387T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 723,324 control chromosomes in the GnomAD database, including 33,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.24 ( 5672 hom., cov: 32)
Exomes 𝑓: 0.30 ( 28164 hom. )
Consequence
ANGPT2
NM_001118887.2 3_prime_UTR
NM_001118887.2 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.137
Publications
9 publications found
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]
MCPH1 Gene-Disease associations (from GenCC):
- microcephaly 1, primary, autosomal recessiveInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- microcephaly with intellectual disabilityInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- autosomal recessive primary microcephalyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- hereditary breast carcinomaInheritance: AD Classification: LIMITED Submitted by: ClinGen
- familial ovarian cancerInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 8-6499714-A-T is Benign according to our data. Variant chr8-6499714-A-T is described in ClinVar as [Benign]. Clinvar id is 1262416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANGPT2 | ENST00000629816.3 | c.*3387T>A | 3_prime_UTR_variant | Exon 9 of 9 | 1 | NM_001118887.2 | ENSP00000486858.2 | |||
MCPH1 | ENST00000344683.10 | c.2137-138A>T | intron_variant | Intron 11 of 13 | 1 | NM_024596.5 | ENSP00000342924.5 |
Frequencies
GnomAD3 genomes AF: 0.241 AC: 36566AN: 151974Hom.: 5676 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
36566
AN:
151974
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.299 AC: 170966AN: 571232Hom.: 28164 Cov.: 7 AF XY: 0.299 AC XY: 91479AN XY: 305510 show subpopulations
GnomAD4 exome
AF:
AC:
170966
AN:
571232
Hom.:
Cov.:
7
AF XY:
AC XY:
91479
AN XY:
305510
show subpopulations
African (AFR)
AF:
AC:
1048
AN:
16556
American (AMR)
AF:
AC:
6519
AN:
33624
Ashkenazi Jewish (ASJ)
AF:
AC:
7534
AN:
19348
East Asian (EAS)
AF:
AC:
2157
AN:
34088
South Asian (SAS)
AF:
AC:
14764
AN:
61644
European-Finnish (FIN)
AF:
AC:
12147
AN:
38844
Middle Eastern (MID)
AF:
AC:
873
AN:
2404
European-Non Finnish (NFE)
AF:
AC:
116570
AN:
333972
Other (OTH)
AF:
AC:
9354
AN:
30752
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
5555
11110
16664
22219
27774
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.240 AC: 36546AN: 152092Hom.: 5672 Cov.: 32 AF XY: 0.237 AC XY: 17596AN XY: 74348 show subpopulations
GnomAD4 genome
AF:
AC:
36546
AN:
152092
Hom.:
Cov.:
32
AF XY:
AC XY:
17596
AN XY:
74348
show subpopulations
African (AFR)
AF:
AC:
2477
AN:
41510
American (AMR)
AF:
AC:
3399
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
AC:
1319
AN:
3470
East Asian (EAS)
AF:
AC:
326
AN:
5174
South Asian (SAS)
AF:
AC:
1002
AN:
4820
European-Finnish (FIN)
AF:
AC:
3227
AN:
10546
Middle Eastern (MID)
AF:
AC:
120
AN:
294
European-Non Finnish (NFE)
AF:
AC:
23827
AN:
67978
Other (OTH)
AF:
AC:
586
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1346
2691
4037
5382
6728
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
487
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Jun 26, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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