Variant rs3020221 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001118887.2(ANGPT2):c.735G>A(p.Gln245Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,613,280 control chromosomes in the GnomAD database, including 109,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.35 ( 9359 hom., cov: 32)

Exomes 𝑓: 0.37 ( 99713 hom. )

Consequence

ANGPT2
NM_001118887.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0810

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 links:

MCPH1 (HGNC:):

MCPH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 8-6521242-C-T is Benign according to our data. Variant chr8-6521242-C-T is described in ClinVar as [Benign]. Clinvar id is 158838.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-6521242-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.081 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPT2	NM_001118887.2 linkuse as main transcript	c.735G>A	p.Gln245Gln	synonymous_variant	4/9	ENST00000629816.3	NP_001112359.1	O15123-3
MCPH1	NM_024596.5 linkuse as main transcript	c.2214+21313C>T		intron_variant		ENST00000344683.10	NP_078872.3	Q8NEM0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPT2	ENST00000629816.3 linkuse as main transcript	c.735G>A	p.Gln245Gln	synonymous_variant	4/9	1	NM_001118887.2	ENSP00000486858.2		O15123-3
MCPH1	ENST00000344683.10 linkuse as main transcript	c.2214+21313C>T		intron_variant		1	NM_024596.5	ENSP00000342924.5		Q8NEM0-1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52902

AN:

151912

Hom.:

9357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.379

Gnomad OTH

AF:

0.374

GnomAD3 exomes

AF:

0.340

AC:

85543

AN:

251312

Hom.:

15052

AF XY:

0.347

AC XY:

47175

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.245

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.240

Gnomad SAS exome

AF:

0.345

Gnomad FIN exome

AF:

0.332

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.367

AC:

536096

AN:

1461250

Hom.:

99713

Cov.:

AF XY:

0.368

AC XY:

267566

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.338

Gnomad4 AMR exome

AF:

0.248

Gnomad4 ASJ exome

AF:

0.378

Gnomad4 EAS exome

AF:

0.243

Gnomad4 SAS exome

AF:

0.350

Gnomad4 FIN exome

AF:

0.336

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.348

AC:

52927

AN:

152030

Hom.:

9359

Cov.:

AF XY:

0.344

AC XY:

25555

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.335

Gnomad4 AMR

AF:

0.285

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.238

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.379

Gnomad4 OTH

AF:

0.370

Alfa

AF:

0.375

Hom.:

14276

Bravo

AF:

0.345

Asia WGS

AF:

0.267

AC:

927

AN:

3476

EpiCase

AF:

0.393

EpiControl

AF:

0.391

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.3

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over