2-48440812-CGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant names:

• chr2-48440812-C-CGCGGCGGCG
• rs34664331
• NM_001135629.3:c.-127_-119dupGGCGGCGGC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001135629.3(PPP1R21):​c.-127_-119dupGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 626,722 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0040 (13 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.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0035 (530/151632) while in subpopulation EAS AF = 0.0179 (91/5076). AF 95% confidence interval is 0.015. There are 0 homozygotes in GnomAd4. There are 284 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R21	NM_001135629.3	c.-127_-119dupGGCGGCGGC		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.-127_-119dupGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 22	1	NM_001135629.3	ENSP00000294952.8

Frequencies

GnomAD3 genomes AF: 0.00348 AC: 527 AN: 151514 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00336

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00420

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.000477

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00261

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00403 AC: 1913 AN: 475090 Hom.: 13 Cov.: 4 AF XY: 0.00426 AC XY: 1089 AN XY: 255904

African (AFR) AF: 0.00379 AC: 38 AN: 10020

American (AMR) AF: 0.00573 AC: 103 AN: 17980

Ashkenazi Jewish (ASJ) AF: 0.00227 AC: 34 AN: 14962

East Asian (EAS) AF: 0.0174 AC: 440 AN: 25266

South Asian (SAS) AF: 0.00921 AC: 458 AN: 49730

European-Finnish (FIN) AF: 0.000590 AC: 25 AN: 42394

Middle Eastern (MID) AF: 0.00762 AC: 16 AN: 2100

European-Non Finnish (NFE) AF: 0.00240 AC: 686 AN: 286212

Other (OTH) AF: 0.00428 AC: 113 AN: 26426

GnomAD4 genome AF: 0.00350 AC: 530 AN: 151632 Hom.: 0 Cov.: 24 AF XY: 0.00383 AC XY: 284 AN XY: 74110

African (AFR) AF: 0.00340 AC: 141 AN: 41454

American (AMR) AF: 0.00420 AC: 64 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3462

East Asian (EAS) AF: 0.0179 AC: 91 AN: 5076

South Asian (SAS) AF: 0.00789 AC: 38 AN: 4818

European-Finnish (FIN) AF: 0.000477 AC: 5 AN: 10492

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.00261 AC: 177 AN: 67764

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.000868 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;