dbSNP rs4682314: PLCXD2:c.*33+54063C>A (chr3-111786766-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001134437.2(PHLDB2):c.-49+54063C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,816 control chromosomes in the GnomAD database, including 17,364 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 17364 hom., cov: 31)

Consequence

PHLDB2
NM_001134437.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.786

Publications

3 publications found

Variant links:

Genes affected

PLCXD2 (HGNC:26462): (phosphatidylinositol specific phospholipase C X domain containing 2) Predicted to enable phosphoric diester hydrolase activity. Predicted to be involved in lipid catabolic process and signal transduction. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PLCXD2 links:

PHLDB2 (HGNC:29573): (pleckstrin homology like domain family B member 2) Enables cadherin binding activity. Involved in several processes, including negative regulation of focal adhesion assembly; regulation of cytoskeleton organization; and regulation of embryonic development. Located in several cellular components, including basal cortex; cell leading edge; and intermediate filament cytoskeleton. Colocalizes with focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

PHLDB2 links:

LOC107984087 (HGNC:):

LOC107984087 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134437.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHLDB2	NM_001134437.2		c.-49+54063C>A		intron	N/A	NP_001127909.1	Q86SQ0-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLCXD2	ENST00000477665.2	TSL:1	c.*33+54063C>A	intron	N/A	ENSP00000420686.1	Q0VAA5-1
PLCXD2	ENST00000393934.7	TSL:1	c.867-59055C>A	intron	N/A	ENSP00000377511.3	Q0VAA5-2
PHLDB2	ENST00000878043.1		c.-130+54063C>A	intron	N/A	ENSP00000548102.1

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65439

AN:

151698

Hom.:

17346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.634

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.646

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.474

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.431

AC:

65458

AN:

151816

Hom.:

17364

Cov.:

AF XY:

0.440

AC XY:

32627

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.117

AC:

4828

AN:

41442

American (AMR)

AF:

0.523

AC:

7958

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.634

AC:

2201

AN:

3472

East Asian (EAS)

AF:

0.774

AC:

3976

AN:

5134

South Asian (SAS)

AF:

0.648

AC:

3122

AN:

4820

European-Finnish (FIN)

AF:

0.550

AC:

5782

AN:

10512

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.530

AC:

36020

AN:

67904

Other (OTH)

AF:

0.480

AC:

1012

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1553

3105

4658

6210

7763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.501

Hom.:

64090

Bravo

AF:

0.414

Asia WGS

AF:

0.670

AC:

2332

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over