rs2029721

Variant names:

• chr12-62755564-G-A
• rs2029721
• NM_020700.2:c.870-17978C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020700.2(PPM1H):​c.870-17978C>T variant causes a intron change. The variant allele was found at a frequency of 0.332 in 653,130 control chromosomes in the GnomAD database, including 38,593 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (7471 hom., cov: 31)
  • Exomes 𝑓: 0.34 (31122 hom.)
• Consequence: PPM1H NM_020700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.97
• Publications: 3 publications found

Genes affected

PPM1H (HGNC:18583): (protein phosphatase, Mg2+/Mn2+ dependent 1H) Enables identical protein binding activity and phosphoprotein phosphatase activity. Predicted to be involved in protein dephosphorylation. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GAPDHP44 (HGNC:37801): (glyceraldehyde 3 phosphate dehydrogenase pseudogene 44)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.870-17978C>T		intron_variant	Intron 4 of 9	ENST00000228705.7	NP_065751.1
GAPDHP44		n.62755564G>A		intragenic_variant
PPM1H	XM_011538578.3	c.756-17978C>T		intron_variant	Intron 4 of 9		XP_011536880.1
PPM1H	XM_017019676.3	c.870-17978C>T		intron_variant	Intron 4 of 8		XP_016875165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7	c.870-17978C>T		intron_variant	Intron 4 of 9	1	NM_020700.2	ENSP00000228705.5
GAPDHP44	ENST00000513513.1	n.338G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
PPM1H	ENST00000551519.1	n.260-17978C>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43880 AN: 151888 Hom.: 7471 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.345 AC: 172767 AN: 501124 Hom.: 31122 Cov.: 2 AF XY: 0.341 AC XY: 92932 AN XY: 272180

African (AFR) AF: 0.112 AC: 1629 AN: 14600

American (AMR) AF: 0.377 AC: 11627 AN: 30820

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 3881 AN: 14100

East Asian (EAS) AF: 0.219 AC: 7101 AN: 32442

South Asian (SAS) AF: 0.280 AC: 15675 AN: 56042

European-Finnish (FIN) AF: 0.424 AC: 13528 AN: 31912

Middle Eastern (MID) AF: 0.256 AC: 568 AN: 2216

European-Non Finnish (NFE) AF: 0.376 AC: 109772 AN: 292164

Other (OTH) AF: 0.335 AC: 8986 AN: 26828

GnomAD4 genome AF: 0.289 AC: 43881 AN: 152006 Hom.: 7471 Cov.: 31 AF XY: 0.289 AC XY: 21506 AN XY: 74304

African (AFR) AF: 0.113 AC: 4670 AN: 41504

American (AMR) AF: 0.326 AC: 4983 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 997 AN: 3462

East Asian (EAS) AF: 0.205 AC: 1058 AN: 5162

South Asian (SAS) AF: 0.284 AC: 1369 AN: 4816

European-Finnish (FIN) AF: 0.433 AC: 4566 AN: 10546

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25129 AN: 67926

Other (OTH) AF: 0.302 AC: 637 AN: 2112

Alfa AF: 0.342 Hom.: 1242

Bravo AF: 0.275

Asia WGS AF: 0.240 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.1
DANN	Benign	0.78
PhyloP100		7.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2029721; hg19: chr12-63149344;