rs861818

Variant names:

• chr22-21697294-G-T
• rs861818
• NM_014337.4:c.*1804G>T

Variant summary

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

The NM_014337.4(PPIL2):​c.*1804G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 361,046 control chromosomes in the GnomAD database, including 5,092 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 0.18 (2552 hom., cov: 32)
  • Exomes 𝑓: 0.14 (2540 hom.)
• Consequence: PPIL2 NM_014337.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 9 publications found

Genes affected

PPIL2 (HGNC:9261): (peptidylprolyl isomerase like 2) This gene is a member of the cyclophilin family of peptidylprolyl isomerases. The cyclophilins are a highly conserved ubiquitous family, members of which play an important role in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. This protein interacts with the proteinase inhibitor eglin c and is localized in the nucleus. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

YPEL1 (HGNC:12845): (yippee like 1) This gene is located in the region associated with DiGeorge syndrome on chromosome 22. The encoded protein localizes to the centrosome and nucleolus and may play a role in the regulation of cell division. [provided by RefSeq, Feb 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014337.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	NM_014337.4	MANE Select	c.*1804G>T		3_prime_UTR	Exon 20 of 20	NP_055152.1	Q13356-1
	PPIL2	NM_148176.3		c.*391G>T		3_prime_UTR	Exon 21 of 21	NP_680481.1	Q13356-2
	PPIL2	NM_001317996.2		c.*1434G>T		3_prime_UTR	Exon 21 of 21	NP_001304925.1	Q13356-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	ENST00000398831.8	TSL:1 MANE Select	c.*1804G>T		3_prime_UTR	Exon 20 of 20	ENSP00000381812.3	Q13356-1
	PPIL2	ENST00000626352.2	TSL:1	c.*391G>T		3_prime_UTR	Exon 21 of 21	ENSP00000486725.1	Q13356-2
	PPIL2	ENST00000335025.12	TSL:1	c.*554G>T		3_prime_UTR	Exon 21 of 21	ENSP00000334553.7	Q13356-1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26692 AN: 152008 Hom.: 2549 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.144 AC: 30141 AN: 208920 Hom.: 2540 Cov.: 0 AF XY: 0.140 AC XY: 15434 AN XY: 110372

African (AFR) AF: 0.238 AC: 1646 AN: 6928

American (AMR) AF: 0.118 AC: 971 AN: 8204

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 817 AN: 6130

East Asian (EAS) AF: 0.00111 AC: 13 AN: 11666

South Asian (SAS) AF: 0.0897 AC: 2369 AN: 26422

European-Finnish (FIN) AF: 0.209 AC: 2311 AN: 11038

Middle Eastern (MID) AF: 0.143 AC: 136 AN: 948

European-Non Finnish (NFE) AF: 0.160 AC: 20076 AN: 125764

Other (OTH) AF: 0.152 AC: 1802 AN: 11820

GnomAD4 genome AF: 0.176 AC: 26724 AN: 152126 Hom.: 2552 Cov.: 32 AF XY: 0.174 AC XY: 12916 AN XY: 74374

African (AFR) AF: 0.237 AC: 9837 AN: 41470

American (AMR) AF: 0.135 AC: 2060 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.100 AC: 483 AN: 4820

European-Finnish (FIN) AF: 0.205 AC: 2169 AN: 10600

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11141 AN: 67968

Other (OTH) AF: 0.179 AC: 377 AN: 2110

Alfa AF: 0.170 Hom.: 3653

Bravo AF: 0.176

Asia WGS AF: 0.0600 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.74
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs861818; hg19: chr22-22051583;