rs2052584

Positions:

• chr16-71655074-G-A
• chr16-71655074-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PHLPP2	NM_015020.3	c.2585+166C>T		intron_variant		ENST00000568954.5
PHLPP2	NM_001289003.1	c.2384+166C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHLPP2	ENST00000568954.5	c.2585+166C>T		intron_variant		1	NM_015020.3	P2
	ENST00000567077.1	n.48G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128786 AN: 152110 Hom.: 54702 Cov.: 33

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.: 4 AF XY: 0.869 AC XY: 182049 AN XY: 209438

Gnomad4 AFR exome AF: 0.803

Gnomad4 AMR exome AF: 0.916

Gnomad4 ASJ exome AF: 0.919

Gnomad4 EAS exome AF: 0.990

Gnomad4 SAS exome AF: 0.962

Gnomad4 FIN exome AF: 0.855

Gnomad4 NFE exome AF: 0.835

Gnomad4 OTH exome AF: 0.869

GnomAD4 genome AF: 0.846 AC: 128856 AN: 152228 Hom.: 54726 Cov.: 33 AF XY: 0.853 AC XY: 63485 AN XY: 74430

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.967

Gnomad4 FIN AF: 0.872

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.870

Alfa AF: 0.847 Hom.: 9013

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
DANN	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs2052584; hg19: chr16-71688977;