chr6-42989595-C-A

Variant names:

• chr6-42989595-C-A
• rs1771105771
• NM_006245.4:c.28-16C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006245.4(PPP2R5D):​c.28-16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,451,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: PPP2R5D NM_006245.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.218
• 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: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-42989595-C-A is Benign according to our data. Variant chr6-42989595-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2867089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 26 AD gene.

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.28-16C>A		intron	N/A	NP_006236.1	Q14738-1
	PPP2R5D	NM_180976.3		c.28-16C>A		intron	N/A	NP_851307.1	Q14738-2
	PPP2R5D	NM_180977.3		c.27+4891C>A		intron	N/A	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.28-16C>A		intron	N/A	ENSP00000417963.1	Q14738-1
	PPP2R5D	ENST00000394110.7	TSL:1	c.28-16C>A		intron	N/A	ENSP00000377669.3	Q14738-2
	PPP2R5D	ENST00000461010.5	TSL:1	c.27+4891C>A		intron	N/A	ENSP00000420674.1	Q14738-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000179 AC: 26 AN: 1451086 Hom.: 0 Cov.: 30 AF XY: 0.0000180 AC XY: 13 AN XY: 722142

African (AFR) AF: 0.0000301 AC: 1 AN: 33206

American (AMR) AF: 0.00 AC: 0 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 85566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000227 AC: 25 AN: 1103286

Other (OTH) AF: 0.00 AC: 0 AN: 60012

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.60
PhyloP100		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1771105771; hg19: chr6-42957333;