Genetic Variant PATL2:c.1225-2A>G (chr15-44668484-T-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate

The NM_001387263.1(PATL2):c.1225-2A>G variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.0000103 in 1,549,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PATL2
NM_001387263.1 splice_acceptor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

PATL2 (HGNC:33630): (PAT1 homolog 2) Predicted to enable RNA binding activity. Predicted to be involved in P-body assembly and deadenylation-dependent decapping of nuclear-transcribed mRNA. Predicted to act upstream of or within negative regulation of cytoplasmic mRNA processing body assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PATL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.08639706 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-44668484-T-C is Pathogenic according to our data. Variant chr15-44668484-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 1323414.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PATL2	NM_001387263.1 link	c.1225-2A>G		splice_acceptor_variant, intron_variant	Intron 14 of 17	ENST00000682850.1	NP_001374192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PATL2	ENST00000682850.1 link	c.1225-2A>G		splice_acceptor_variant, intron_variant	Intron 14 of 17		NM_001387263.1	ENSP00000508024.1	C9JE40
PATL2	ENST00000558809.1 link	c.2A>G	p.Gln1Arg	missense_variant	Exon 1 of 3	3		ENSP00000453723.1	H0YMS5
PATL2	ENST00000434130.6 link	c.1225-2A>G		splice_acceptor_variant, intron_variant	Intron 12 of 15	5		ENSP00000416673.1	C9JE40
PATL2	ENST00000560780.1 link	c.658-2A>G		splice_acceptor_variant, intron_variant	Intron 11 of 14	2		ENSP00000453695.1	H0YMQ2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1397338

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

689174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000336

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oocyte maturation defect 4

Pathogenic:1

Jan 31, 2020

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Benign

0.97

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Uncertain

0.96

GERP RS

5.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.86

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.86

Position offset: -2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over