NM_001118887.2:c.*3387T>A

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.137

Publications

9 publications found
Variant links:
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 recessive
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • microcephaly with intellectual disability
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • autosomal recessive primary microcephaly
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • hereditary breast carcinoma
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • familial ovarian cancer
    Inheritance: 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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANGPT2NM_001118887.2 linkc.*3387T>A 3_prime_UTR_variant Exon 9 of 9 ENST00000629816.3 NP_001112359.1 O15123-3
MCPH1NM_024596.5 linkc.2137-138A>T intron_variant Intron 11 of 13 ENST00000344683.10 NP_078872.3 Q8NEM0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANGPT2ENST00000629816.3 linkc.*3387T>A 3_prime_UTR_variant Exon 9 of 9 1 NM_001118887.2 ENSP00000486858.2 O15123-3
MCPH1ENST00000344683.10 linkc.2137-138A>T intron_variant Intron 11 of 13 1 NM_024596.5 ENSP00000342924.5 Q8NEM0-1

Frequencies

GnomAD3 genomes
AF:
0.241
AC:
36566
AN:
151974
Hom.:
5676
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0598
Gnomad AMI
AF:
0.289
Gnomad AMR
AF:
0.223
Gnomad ASJ
AF:
0.380
Gnomad EAS
AF:
0.0631
Gnomad SAS
AF:
0.208
Gnomad FIN
AF:
0.306
Gnomad MID
AF:
0.408
Gnomad NFE
AF:
0.351
Gnomad OTH
AF:
0.281
GnomAD4 exome
AF:
0.299
AC:
170966
AN:
571232
Hom.:
28164
Cov.:
7
AF XY:
0.299
AC XY:
91479
AN XY:
305510
show subpopulations
African (AFR)
AF:
0.0633
AC:
1048
AN:
16556
American (AMR)
AF:
0.194
AC:
6519
AN:
33624
Ashkenazi Jewish (ASJ)
AF:
0.389
AC:
7534
AN:
19348
East Asian (EAS)
AF:
0.0633
AC:
2157
AN:
34088
South Asian (SAS)
AF:
0.240
AC:
14764
AN:
61644
European-Finnish (FIN)
AF:
0.313
AC:
12147
AN:
38844
Middle Eastern (MID)
AF:
0.363
AC:
873
AN:
2404
European-Non Finnish (NFE)
AF:
0.349
AC:
116570
AN:
333972
Other (OTH)
AF:
0.304
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

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
862
1724
2586
3448
4310
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.240
AC:
36546
AN:
152092
Hom.:
5672
Cov.:
32
AF XY:
0.237
AC XY:
17596
AN XY:
74348
show subpopulations
African (AFR)
AF:
0.0597
AC:
2477
AN:
41510
American (AMR)
AF:
0.223
AC:
3399
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.380
AC:
1319
AN:
3470
East Asian (EAS)
AF:
0.0630
AC:
326
AN:
5174
South Asian (SAS)
AF:
0.208
AC:
1002
AN:
4820
European-Finnish (FIN)
AF:
0.306
AC:
3227
AN:
10546
Middle Eastern (MID)
AF:
0.408
AC:
120
AN:
294
European-Non Finnish (NFE)
AF:
0.351
AC:
23827
AN:
67978
Other (OTH)
AF:
0.277
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

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
382
764
1146
1528
1910
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.280
Hom.:
836
Bravo
AF:
0.228
Asia WGS
AF:
0.140
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
2.2
DANN
Benign
0.81
PhyloP100
-0.14
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2916716; hg19: chr8-6357235; API