Genetic Variant PHLPP2:c.2585+166C>T (chr16-71655074-G-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_015020.3(PHLPP2):c.2585+166C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 556,132 control chromosomes in the GnomAD database, including 206,723 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 0.85 ( 54726 hom., cov: 33)

Exomes 𝑓: 0.87 ( 151997 hom. )

Consequence

PHLPP2
NM_015020.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

3 publications found

Variant links:

Genes affected

PHLPP2 (HGNC:29149): (PH domain and leucine rich repeat protein phosphatase 2) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Located in several cellular components, including intercellular bridge; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PHLPP2 links:

ENSG00000260185 (HGNC:):

ENSG00000260185 links:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLPP2	NM_015020.3 link	c.2585+166C>T		intron_variant	Intron 17 of 18	ENST00000568954.5	NP_055835.2	Q6ZVD8-1
PHLPP2	NM_001289003.1 link	c.2384+166C>T		intron_variant	Intron 16 of 17		NP_001275932.1	Q6ZVD8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLPP2	ENST00000568954.5 link	c.2585+166C>T		intron_variant	Intron 17 of 18	1	NM_015020.3	ENSP00000457991.1		Q6ZVD8-1

Frequencies

GnomAD3 genomes

AF:

0.847

AC:

128786

AN:

152110

Hom.:

54702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.806

Gnomad AMI

AF:

0.833

Gnomad AMR

AF:

0.903

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.991

Gnomad SAS

AF:

0.967

Gnomad FIN

AF:

0.872

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.831

Gnomad OTH

AF:

0.868

GnomAD4 exome

AF:

0.865

AC:

349481

AN:

403904

Hom.:

151997

Cov.:

AF XY:

0.869

AC XY:

182049

AN XY:

209438

show subpopulations

African (AFR)

AF:

0.803

AC:

9716

AN:

12104

American (AMR)

AF:

0.916

AC:

16309

AN:

17802

Ashkenazi Jewish (ASJ)

AF:

0.919

AC:

11548

AN:

12562

East Asian (EAS)

AF:

0.990

AC:

30289

AN:

30596

South Asian (SAS)

AF:

0.962

AC:

29731

AN:

30912

European-Finnish (FIN)

AF:

0.855

AC:

26837

AN:

31376

Middle Eastern (MID)

AF:

0.895

AC:

1620

AN:

1810

European-Non Finnish (NFE)

AF:

0.835

AC:

202676

AN:

242848

Other (OTH)

AF:

0.869

AC:

20755

AN:

23894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2131

4263

6394

8526

10657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

980

1960

2940

3920

4900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.846

AC:

128856

AN:

152228

Hom.:

54726

Cov.:

AF XY:

0.853

AC XY:

63485

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.805

AC:

33439

AN:

41518

American (AMR)

AF:

0.903

AC:

13806

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

3158

AN:

3472

East Asian (EAS)

AF:

0.991

AC:

5143

AN:

5192

South Asian (SAS)

AF:

0.967

AC:

4669

AN:

4828

European-Finnish (FIN)

AF:

0.872

AC:

9256

AN:

10610

Middle Eastern (MID)

AF:

0.881

AC:

259

AN:

294

European-Non Finnish (NFE)

AF:

0.831

AC:

56534

AN:

68012

Other (OTH)

AF:

0.870

AC:

1836

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

993

1987

2980

3974

4967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.846

Hom.:

9265

Bravo

AF:

0.846

Asia WGS

AF:

0.957

AC:

3325

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

(source)

DANN

Benign

0.74

PhyloP100

-1.4

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over