rs752038217

Variant names:

• chr6-42984690-C-G
• rs752038217
• NM_006245.4:c.13C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-42984690-C-G
• chr6-42984690-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006245.4(PPP2R5D):​c.13C>G​(p.Leu5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L5L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PPP2R5D NM_006245.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

Genes affected

PPP2R5D (HGNC:9312): (protein phosphatase 2 regulatory subunit B'delta) The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a delta isoform of the regulatory subunit B56 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PPP2R5D Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Hogue-Janssens syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10173488).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006245.4. 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
	PPP2R5D	NM_006245.4	MANE Select	c.13C>G	p.Leu5Val	missense	Exon 1 of 16	NP_006236.1	Q14738-1
	PPP2R5D	NM_180976.3		c.13C>G	p.Leu5Val	missense	Exon 1 of 16	NP_851307.1	Q14738-2
	PPP2R5D	NM_180977.3		c.13C>G	p.Leu5Val	missense	Exon 1 of 14	NP_851308.1	Q14738-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5D	ENST00000485511.6	TSL:1 MANE Select	c.13C>G	p.Leu5Val	missense	Exon 1 of 16	ENSP00000417963.1	Q14738-1
	PPP2R5D	ENST00000394110.7	TSL:1	c.13C>G	p.Leu5Val	missense	Exon 1 of 16	ENSP00000377669.3	Q14738-2
	PPP2R5D	ENST00000461010.5	TSL:1	c.13C>G	p.Leu5Val	missense	Exon 1 of 14	ENSP00000420674.1	Q14738-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459566 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726028

African (AFR) AF: 0.00 AC: 0 AN: 33338

American (AMR) AF: 0.00 AC: 0 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 85860

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111126

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.014
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.12
Sift	Benign	0.15	T
Sift4G	Benign	0.57	T
Polyphen		0.17	B
Vest4		0.30
MutPred		0.12		Loss of stability (P = 0.0725)
MVP		0.19
MPC		1.2
ClinPred		0.94	D
GERP RS		4.2
PromoterAI		-0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.16
gMVP		0.073
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs752038217; hg19: chr6-42952428;