Variant X-55006805-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014481.4(APEX2):c.927A>G(p.Ala309Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,210,044 control chromosomes in the GnomAD database, including 57 homozygotes. There are 893 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 39 hom., 457 hem., cov: 22)

Exomes 𝑓: 0.0015 ( 18 hom. 436 hem. )

Consequence

APEX2
NM_014481.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.213

Variant links:

Genes affected

APEX2 (HGNC:17889): (apurinic/apyrimidinic endodeoxyribonuclease 2) Apurinic/apyrimidinic (AP) sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication so the cell contains systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site. This gene encodes a protein shown to have a weak class II AP endonuclease activity. Most of the encoded protein is located in the nucleus but some is also present in mitochondria. This protein may play an important role in both nuclear and mitochondrial base excision repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]

APEX2 links:

APEX2 (HGNC:):

APEX2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-55006805-A-G is Benign according to our data. Variant chrX-55006805-A-G is described in ClinVar as [Benign]. Clinvar id is 782675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.213 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APEX2	NM_014481.4 linkuse as main transcript	c.927A>G	p.Ala309Ala	synonymous_variant	6/6	ENST00000374987.4	NP_055296.2	Q9UBZ4E5KN95
APEX2	NM_001271748.2 linkuse as main transcript	c.414A>G	p.Ala138Ala	synonymous_variant	5/5		NP_001258677.1	B7ZA71B4DWI9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APEX2	ENST00000374987.4 linkuse as main transcript	c.927A>G	p.Ala309Ala	synonymous_variant	6/6	1	NM_014481.4	ENSP00000364126.3		Q9UBZ4
APEX2	ENST00000471758.1 linkuse as main transcript	n.*48A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

1675

AN:

111930

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

456

AN XY:

34112

show subpopulations

Gnomad AFR

AF:

0.0525

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00433

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000370

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000564

Gnomad OTH

AF:

0.00863

GnomAD3 exomes

AF:

0.00420

AC:

766

AN:

182337

Hom.:

AF XY:

0.00272

AC XY:

182

AN XY:

66843

show subpopulations

Gnomad AFR exome

AF:

0.0532

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000530

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000861

Gnomad OTH exome

AF:

0.00266

GnomAD4 exome

AF:

0.00148

AC:

1622

AN:

1098062

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

436

AN XY:

363420

show subpopulations

Gnomad4 AFR exome

AF:

0.0512

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000740

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000131

Gnomad4 OTH exome

AF:

0.00343

GnomAD4 genome

AF:

0.0150

AC:

1678

AN:

111982

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

457

AN XY:

34174

show subpopulations

Gnomad4 AFR

AF:

0.0525

Gnomad4 AMR

AF:

0.00433

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000371

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00834

Hom.:

Bravo

AF:

0.0172

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.4

DANN

Benign

0.75

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