Variant X-55002258-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014481.4(APEX2):c.249C>T(p.Ala83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,193,051 control chromosomes in the GnomAD database, including 63 homozygotes. There are 3,697 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 4 hom., 202 hem., cov: 23)

Exomes 𝑓: 0.010 ( 59 hom. 3495 hem. )

Consequence

APEX2
NM_014481.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.957

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant X-55002258-C-T is Benign according to our data. Variant chrX-55002258-C-T is described in ClinVar as [Benign]. Clinvar id is 719560.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-55002258-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APEX2	NM_014481.4 linkuse as main transcript	c.249C>T	p.Ala83=	synonymous_variant	3/6	ENST00000374987.4
APEX2	NM_001271748.2 linkuse as main transcript	c.-92+629C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APEX2	ENST00000374987.4 linkuse as main transcript	c.249C>T	p.Ala83=	synonymous_variant	3/6	1	NM_014481.4	P1
APEX2	ENST00000471758.1 linkuse as main transcript	n.271+629C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00708

AC:

796

AN:

112364

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

203

AN XY:

34528

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000737

Gnomad FIN

AF:

0.000969

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.00635

AC:

1006

AN:

158422

Hom.:

AF XY:

0.00555

AC XY:

267

AN XY:

48074

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00668

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00115

Gnomad FIN exome

AF:

0.00183

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.00736

GnomAD4 exome

AF:

0.0104

AC:

11287

AN:

1080633

Hom.:

Cov.:

AF XY:

0.00995

AC XY:

3495

AN XY:

351239

show subpopulations

Gnomad4 AFR exome

AF:

0.00162

Gnomad4 AMR exome

AF:

0.00701

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000896

Gnomad4 FIN exome

AF:

0.00215

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.00789

GnomAD4 genome

AF:

0.00707

AC:

795

AN:

112418

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

202

AN XY:

34592

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000740

Gnomad4 FIN

AF:

0.000969

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.0117

Alfa

AF:

0.00658

Hom.:

Bravo

AF:

0.00778

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.5

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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