chr2-48440812-C-CGCGGCGGCGGCGGCGGCG

Variant names:

• chr2-48440812-C-CGCGGCGGCGGCGGCGGCG
• rs34664331
• NM_001135629.3:c.-136_-119dupGGCGGCGGCGGCGGCGGC

Variant summary

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

The NM_001135629.3(PPP1R21):​c.-136_-119dupGGCGGCGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000319 in 626,744 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000040 (1 hom., cov: 24)
  • Exomes 𝑓: 0.000029 (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 mid. GnomAdExome4 allele frequency = 0.0000295 (14/475112) while in subpopulation MID AF = 0.00143 (3/2102). AF 95% confidence interval is 0.000389. There are 0 homozygotes in GnomAdExome4. There are 9 alleles in the male GnomAdExome4 subpopulation. Median coverage is 4. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R21	NM_001135629.3	c.-136_-119dupGGCGGCGGCGGCGGCGGC		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.-136_-119dupGGCGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 22	1	NM_001135629.3	ENSP00000294952.8

Frequencies

GnomAD3 genomes AF: 0.0000396 AC: 6 AN: 151514 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000295 AC: 14 AN: 475112 Hom.: 0 Cov.: 4 AF XY: 0.0000352 AC XY: 9 AN XY: 255922

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: 0.00 AC: 0 AN: 25270

South Asian (SAS) AF: 0.0000402 AC: 2 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: 0.0000105 AC: 3 AN: 286220

Other (OTH) AF: 0.000227 AC: 6 AN: 26432

GnomAD4 genome AF: 0.0000396 AC: 6 AN: 151632 Hom.: 1 Cov.: 24 AF XY: 0.0000405 AC XY: 3 AN XY: 74110

African (AFR) AF: 0.00 AC: 0 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: 0.000197 AC: 1 AN: 5076

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

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

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

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67764

Other (OTH) AF: 0.00 AC: 0 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;