2-48440812-CGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCG

Variant names:

• chr2-48440812-C-CGCGGCG
• rs34664331
• NM_001135629.3:c.-124_-119dupGGCGGC

Variant summary

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

The NM_001135629.3(PPP1R21):​c.-124_-119dupGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 626,614 control chromosomes in the GnomAD database, including 528 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.042 (157 hom., cov: 24)
  • Exomes 𝑓: 0.040 (371 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 (SAS) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R21	NM_001135629.3	c.-124_-119dupGGCGGC		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.-124_-119dupGGCGGC		5_prime_UTR_variant	Exon 1 of 22	1	NM_001135629.3	ENSP00000294952.8

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6383 AN: 151494 Hom.: 157 Cov.: 24

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0661

Gnomad EAS AF: 0.00806

Gnomad SAS AF: 0.0873

Gnomad FIN AF: 0.00858

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.0440

GnomAD4 exome AF: 0.0404 AC: 19170 AN: 475002 Hom.: 371 Cov.: 4 AF XY: 0.0431 AC XY: 11020 AN XY: 255858

African (AFR) AF: 0.0614 AC: 615 AN: 10014

American (AMR) AF: 0.0460 AC: 827 AN: 17974

Ashkenazi Jewish (ASJ) AF: 0.0638 AC: 955 AN: 14958

East Asian (EAS) AF: 0.00511 AC: 129 AN: 25268

South Asian (SAS) AF: 0.0922 AC: 4583 AN: 49714

European-Finnish (FIN) AF: 0.0139 AC: 588 AN: 42390

Middle Eastern (MID) AF: 0.0890 AC: 187 AN: 2102

European-Non Finnish (NFE) AF: 0.0354 AC: 10129 AN: 286160

Other (OTH) AF: 0.0438 AC: 1157 AN: 26422

GnomAD4 genome AF: 0.0421 AC: 6388 AN: 151612 Hom.: 157 Cov.: 24 AF XY: 0.0424 AC XY: 3143 AN XY: 74098

African (AFR) AF: 0.0576 AC: 2387 AN: 41446

American (AMR) AF: 0.0400 AC: 610 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0661 AC: 229 AN: 3462

East Asian (EAS) AF: 0.00808 AC: 41 AN: 5076

South Asian (SAS) AF: 0.0866 AC: 417 AN: 4818

European-Finnish (FIN) AF: 0.00858 AC: 90 AN: 10492

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0364 AC: 2465 AN: 67754

Other (OTH) AF: 0.0436 AC: 92 AN: 2112

Alfa AF: 0.00738 Hom.: 56

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=300/0	polymorphism

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;