rs3739390

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001118887.2(ANGPT2):c.-35G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,550,278 control chromosomes in the GnomAD database, including 3,146 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 0.060 ( 333 hom., cov: 29)

Exomes 𝑓: 0.061 ( 2813 hom. )

Consequence

ANGPT2
NM_001118887.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00600

Publications

22 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]

ANGPT2 links:

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: Unknown Classification: LIMITED Submitted by: ClinGen
familial ovarian cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

MCPH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001118887.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANGPT2	NM_001118887.2	MANE Select	c.-35G>C	5_prime_UTR	Exon 1 of 9	NP_001112359.1	O15123-3
MCPH1	NM_024596.5	MANE Select	c.2215-58485C>G	intron	N/A	NP_078872.3	Q8NEM0-1
ANGPT2	NM_001147.3		c.-35G>C	5_prime_UTR	Exon 1 of 9	NP_001138.1	O15123-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANGPT2	ENST00000629816.3	TSL:1 MANE Select	c.-35G>C	5_prime_UTR	Exon 1 of 9	ENSP00000486858.2	O15123-3
ANGPT2	ENST00000325203.9	TSL:1	c.-35G>C	5_prime_UTR	Exon 1 of 9	ENSP00000314897.5	O15123-1
ANGPT2	ENST00000523120.2	TSL:1	c.-35G>C	5_prime_UTR	Exon 1 of 8	ENSP00000428023.1	E7EVQ3

Frequencies

GnomAD3 genomes

AF:

0.0604

AC:

9189

AN:

152132

Hom.:

332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0536

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0687

Gnomad ASJ

AF:

0.0988

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.0845

Gnomad FIN

AF:

0.0482

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0561

Gnomad OTH

AF:

0.0651

GnomAD2 exomes

AF:

0.0668

AC:

14512

AN:

217262

AF XY:

0.0676

show subpopulations

Gnomad AFR exome

AF:

0.0527

Gnomad AMR exome

AF:

0.0718

Gnomad ASJ exome

AF:

0.0928

Gnomad EAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0480

Gnomad NFE exome

AF:

0.0535

Gnomad OTH exome

AF:

0.0681

GnomAD4 exome

AF:

0.0613

AC:

85672

AN:

1398028

Hom.:

2813

Cov.:

AF XY:

0.0620

AC XY:

42528

AN XY:

685772

show subpopulations

African (AFR)

AF:

0.0581

AC:

1883

AN:

32386

American (AMR)

AF:

0.0695

AC:

2917

AN:

41956

Ashkenazi Jewish (ASJ)

AF:

0.0877

AC:

2006

AN:

22868

East Asian (EAS)

AF:

0.104

AC:

4033

AN:

38766

South Asian (SAS)

AF:

0.0912

AC:

6992

AN:

76644

European-Finnish (FIN)

AF:

0.0448

AC:

2245

AN:

50130

Middle Eastern (MID)

AF:

0.0773

AC:

412

AN:

5328

European-Non Finnish (NFE)

AF:

0.0571

AC:

61252

AN:

1072386

Other (OTH)

AF:

0.0683

AC:

3932

AN:

57564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4313

8626

12940

17253

21566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2458

4916

7374

9832

12290

<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:

0.0604

AC:

9198

AN:

152250

Hom.:

333

Cov.:

AF XY:

0.0615

AC XY:

4580

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0535

AC:

2223

AN:

41552

American (AMR)

AF:

0.0690

AC:

1056

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0988

AC:

343

AN:

3472

East Asian (EAS)

AF:

0.121

AC:

627

AN:

5166

South Asian (SAS)

AF:

0.0850

AC:

410

AN:

4826

European-Finnish (FIN)

AF:

0.0482

AC:

511

AN:

10598

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0561

AC:

3816

AN:

68014

Other (OTH)

AF:

0.0649

AC:

137

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

436

871

1307

1742

2178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0586

Hom.:

Bravo

AF:

0.0613

Asia WGS

AF:

0.0770

AC:

268

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.0060

PromoterAI

0.025

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over