2-48440812-CGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant names:

• chr2-48440812-C-CGCGGCGGCGGCGGCG
• rs34664331
• NM_001135629.3:c.-133_-119dupGGCGGCGGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001135629.3(PPP1R21):​c.-133_-119dupGGCGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000782 in 626,746 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000065 (0 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000119 (18/151632) while in subpopulation EAS AF = 0.000788 (4/5076). AF 95% confidence interval is 0.000269. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R21	NM_001135629.3	c.-133_-119dupGGCGGCGGCGGCGGC		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.-133_-119dupGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 22	1	NM_001135629.3	ENSP00000294952.8

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 18 AN: 151514 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000786

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000652 AC: 31 AN: 475114 Hom.: 0 Cov.: 4 AF XY: 0.0000742 AC XY: 19 AN XY: 255924

African (AFR) AF: 0.00 AC: 0 AN: 10020

American (AMR) AF: 0.00 AC: 0 AN: 17980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14962

East Asian (EAS) AF: 0.000158 AC: 4 AN: 25270

South Asian (SAS) AF: 0.000201 AC: 10 AN: 49732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42394

Middle Eastern (MID) AF: 0.00143 AC: 3 AN: 2102

European-Non Finnish (NFE) AF: 0.0000175 AC: 5 AN: 286222

Other (OTH) AF: 0.000340 AC: 9 AN: 26432

GnomAD4 genome AF: 0.000119 AC: 18 AN: 151632 Hom.: 0 Cov.: 24 AF XY: 0.0000810 AC XY: 6 AN XY: 74110

African (AFR) AF: 0.000217 AC: 9 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000788 AC: 4 AN: 5076

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67764

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00 Hom.: 56

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

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;