NM_006244.4:c.72A>C

Variant names:

• chr11-64925806-A-C
• rs1024487131
• NM_006244.4:c.72A>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_006244.4(PPP2R5B):​c.72A>C​(p.Pro24Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP2R5B NM_006244.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.431
• Publications: 0 publications found

Genes affected

PPP2R5B (HGNC:9310): (protein phosphatase 2 regulatory subunit B'beta) 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 beta isoform of the regulatory subunit B56 subfamily. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 11-64925806-A-C is Benign according to our data. Variant chr11-64925806-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3388194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.431 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006244.4. 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
	PPP2R5B	NM_006244.4	MANE Select	c.72A>C	p.Pro24Pro	synonymous	Exon 2 of 14	NP_006235.1	Q15173-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5B	ENST00000164133.7	TSL:1 MANE Select	c.72A>C	p.Pro24Pro	synonymous	Exon 2 of 14	ENSP00000164133.2	Q15173-1
	PPP2R5B	ENST00000872729.1		c.72A>C	p.Pro24Pro	synonymous	Exon 2 of 14	ENSP00000542788.1
	PPP2R5B	ENST00000872717.1		c.72A>C	p.Pro24Pro	synonymous	Exon 4 of 16	ENSP00000542776.1

Frequencies

GnomAD3 genomes AF: 0.000814 AC: 63 AN: 77412 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000925

Gnomad AMI AF: 0.00644

Gnomad AMR AF: 0.000528

Gnomad ASJ AF: 0.000486

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00205

Gnomad FIN AF: 0.000240

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000789

Gnomad OTH AF: 0.00189

GnomAD2 exomes AF: 0.000249 AC: 50 AN: 200652 AF XY: 0.000224

Gnomad AFR exome AF: 0.000169

Gnomad AMR exome AF: 0.000540

Gnomad ASJ exome AF: 0.000116

Gnomad EAS exome AF: 0.000571

Gnomad FIN exome AF: 0.000286

Gnomad NFE exome AF: 0.000155

Gnomad OTH exome AF: 0.000212

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000474 AC: 550 AN: 1160970 Hom.: 0 Cov.: 34 AF XY: 0.000485 AC XY: 277 AN XY: 571156

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000336 AC: 9 AN: 26760

American (AMR) AF: 0.00109 AC: 36 AN: 32912

Ashkenazi Jewish (ASJ) AF: 0.000655 AC: 12 AN: 18318

East Asian (EAS) AF: 0.00159 AC: 38 AN: 23956

South Asian (SAS) AF: 0.000769 AC: 48 AN: 62430

European-Finnish (FIN) AF: 0.00276 AC: 82 AN: 29756

Middle Eastern (MID) AF: 0.000948 AC: 3 AN: 3166

European-Non Finnish (NFE) AF: 0.000314 AC: 289 AN: 919496

Other (OTH) AF: 0.000747 AC: 33 AN: 44176

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000814 AC: 63 AN: 77418 Hom.: 0 Cov.: 24 AF XY: 0.000583 AC XY: 22 AN XY: 37762

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000923 AC: 18 AN: 19498

American (AMR) AF: 0.000528 AC: 4 AN: 7576

Ashkenazi Jewish (ASJ) AF: 0.000486 AC: 1 AN: 2056

East Asian (EAS) AF: 0.00 AC: 0 AN: 3214

South Asian (SAS) AF: 0.00206 AC: 5 AN: 2424

European-Finnish (FIN) AF: 0.000240 AC: 1 AN: 4160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 176

European-Non Finnish (NFE) AF: 0.000789 AC: 29 AN: 36776

Other (OTH) AF: 0.00187 AC: 2 AN: 1072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0148 Hom.: 0

ClinVar

ClinVar submissions

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
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1024487131; hg19: chr11-64693278; COSMIC: COSV51209915; COSMIC: COSV51209915;