2-48440812-CGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCG

Variant names:

• chr2-48440812-C-CGCG
• rs34664331
• NM_001135629.3:c.-121_-119dupGGC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001135629.3(PPP1R21):​c.-121_-119dupGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 625,792 control chromosomes in the GnomAD database, including 4,472 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1618 hom., cov: 24)
  • Exomes 𝑓: 0.11 (2854 hom.)
• Consequence: PPP1R21 NM_001135629.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 4 publications found

Genes affected

PPP1R21 (HGNC:30595): (protein phosphatase 1 regulatory subunit 21) Located in early endosome. [provided by Alliance of Genome Resources, Apr 2022]

PPP1R21-DT (HGNC:55206): (PPP1R21 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R21	NM_001135629.3	c.-121_-119dupGGC		5_prime_UTR_variant	Exon 1 of 22	ENST00000294952.13	NP_001129101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R21	ENST00000294952.13	c.-121_-119dupGGC		5_prime_UTR_variant	Exon 1 of 22	1	NM_001135629.3	ENSP00000294952.8

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17781 AN: 151474 Hom.: 1607 Cov.: 24

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.114 AC: 54185 AN: 474200 Hom.: 2854 Cov.: 4 AF XY: 0.112 AC XY: 28536 AN XY: 255362

African (AFR) AF: 0.0584 AC: 585 AN: 10012

American (AMR) AF: 0.337 AC: 6037 AN: 17922

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 939 AN: 14934

East Asian (EAS) AF: 0.276 AC: 6956 AN: 25234

South Asian (SAS) AF: 0.110 AC: 5433 AN: 49484

European-Finnish (FIN) AF: 0.205 AC: 8691 AN: 42302

Middle Eastern (MID) AF: 0.0377 AC: 79 AN: 2096

European-Non Finnish (NFE) AF: 0.0793 AC: 22675 AN: 285848

Other (OTH) AF: 0.106 AC: 2790 AN: 26368

GnomAD4 genome AF: 0.118 AC: 17817 AN: 151592 Hom.: 1618 Cov.: 24 AF XY: 0.127 AC XY: 9415 AN XY: 74084

African (AFR) AF: 0.0633 AC: 2622 AN: 41450

American (AMR) AF: 0.270 AC: 4114 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 202 AN: 3462

East Asian (EAS) AF: 0.277 AC: 1406 AN: 5076

South Asian (SAS) AF: 0.124 AC: 597 AN: 4818

European-Finnish (FIN) AF: 0.237 AC: 2484 AN: 10472

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0881 AC: 5967 AN: 67760

Other (OTH) AF: 0.107 AC: 225 AN: 2112

Alfa AF: 0.0573 Hom.: 56

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=299/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs34664331; hg19: chr2-48667951;