Variant chr15-64854917-C-G 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_025201.5(PLEKHO2):c.163-4C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,610,736 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 40 hom. )

Consequence

PLEKHO2
NM_025201.5 splice_region, intron

Scores

Splicing: ADA: 0.00006294

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0130

Variant links:

Genes affected

PLEKHO2 (HGNC:30026): (pleckstrin homology domain containing O2) Predicted to act upstream of or within macrophage apoptotic process. Predicted to be located in extracellular region and ficolin-1-rich granule lumen. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHO2 links:

ENSG00000249240 (HGNC:):

ENSG00000249240 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 15-64854917-C-G is Benign according to our data. Variant chr15-64854917-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2645446.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHO2	NM_025201.5 linkuse as main transcript	c.163-4C>G		splice_region_variant, intron_variant		ENST00000323544.5	NP_079477.2	Q8TD55-1
PLEKHO2	NM_001195059.2 linkuse as main transcript	c.13-4C>G		splice_region_variant, intron_variant			NP_001181988.1	Q8TD55-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PLEKHO2	ENST00000323544.5 linkuse as main transcript	c.163-4C>G	splice_region_variant, intron_variant	1	NM_025201.5	ENSP00000326706.4	Q8TD55-1
PLEKHO2	ENST00000616065.4 linkuse as main transcript	c.13-4C>G	splice_region_variant, intron_variant	1		ENSP00000483505.1	Q8TD55-2
ENSG00000249240	ENST00000437723.1 linkuse as main transcript	c.163-4C>G	splice_region_variant, intron_variant	5		ENSP00000397942.1	C9J4A7
ENSG00000249240	ENST00000502574.1 linkuse as main transcript	n.297-4C>G	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00374

AC:

570

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00725

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00638

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00500

AC:

1249

AN:

249594

Hom.:

AF XY:

0.00504

AC XY:

680

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.000747

Gnomad AMR exome

AF:

0.000697

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00638

Gnomad NFE exome

AF:

0.00926

Gnomad OTH exome

AF:

0.00459

GnomAD4 exome

AF:

0.00600

AC:

8750

AN:

1458404

Hom.:

Cov.:

AF XY:

0.00568

AC XY:

4122

AN XY:

725578

show subpopulations

Gnomad4 AFR exome

AF:

0.000958

Gnomad4 AMR exome

AF:

0.000762

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00778

Gnomad4 NFE exome

AF:

0.00722

Gnomad4 OTH exome

AF:

0.00413

GnomAD4 genome

AF:

0.00374

AC:

570

AN:

152332

Hom.:

Cov.:

AF XY:

0.00377

AC XY:

281

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00725

Gnomad4 NFE

AF:

0.00638

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00405

Hom.:

Bravo

AF:

0.00332

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00398

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

PLEKHO2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.63

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000063

dbscSNV1_RF

Benign

0.0

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