Variant rs6559167 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000629816.3(ANGPT2):c.408G>T(p.Ala136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,613,718 control chromosomes in the GnomAD database, including 78,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A136A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.29 ( 6737 hom., cov: 30)

Exomes 𝑓: 0.31 ( 71562 hom. )

Consequence

ANGPT2
ENST00000629816.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.49

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:

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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=-0.73).

BP6

Variant 8-6532368-C-A is Benign according to our data. Variant chr8-6532368-C-A is described in ClinVar as [Benign]. Clinvar id is 158839.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-6532368-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 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.408G>T	p.Ala136=	synonymous_variant	2/9	ENST00000629816.3	NP_001112359.1
MCPH1	NM_024596.5 linkuse as main transcript	c.2214+32439C>A		intron_variant		ENST00000344683.10	NP_078872.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPT2	ENST00000629816.3 linkuse as main transcript	c.408G>T	p.Ala136=	synonymous_variant	2/9	1	NM_001118887.2	ENSP00000486858	P4	O15123-3
MCPH1	ENST00000344683.10 linkuse as main transcript	c.2214+32439C>A		intron_variant		1	NM_024596.5	ENSP00000342924	P1	Q8NEM0-1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44577

AN:

151794

Hom.:

6737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.330

GnomAD3 exomes

AF:

0.300

AC:

75368

AN:

251380

Hom.:

11629

AF XY:

0.302

AC XY:

41024

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.325

Gnomad EAS exome

AF:

0.400

Gnomad SAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.321

GnomAD4 exome

AF:

0.310

AC:

453601

AN:

1461806

Hom.:

71562

Cov.:

AF XY:

0.310

AC XY:

225351

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.328

Gnomad4 EAS exome

AF:

0.418

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.280

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.293

AC:

44580

AN:

151912

Hom.:

6737

Cov.:

AF XY:

0.291

AC XY:

21597

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.241

Gnomad4 AMR

AF:

0.288

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.403

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.285

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.289

Hom.:

1003

EpiCase

AF:

0.333

EpiControl

AF:

0.326

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

-0.73

CADD

Benign

0.051

DANN

Benign

0.75

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

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