Variant chr15-44669869-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001387263.1(PATL2):c.784C>T(p.Arg262Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000572 in 1,399,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

PATL2
NM_001387263.1 stop_gained

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 6.46

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 Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-44669869-G-A is Pathogenic according to our data. Variant chr15-44669869-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 444047.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-44669869-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATL2	NM_001387263.1 linkuse as main transcript	c.784C>T	p.Arg262Ter	stop_gained	11/18	ENST00000682850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PATL2	ENST00000682850.1 linkuse as main transcript	c.784C>T	p.Arg262Ter	stop_gained	11/18		NM_001387263.1	A2
PATL2	ENST00000434130.6 linkuse as main transcript	c.784C>T	p.Arg262Ter	stop_gained	9/16	5		A2
PATL2	ENST00000560780.1 linkuse as main transcript	c.217C>T	p.Arg73Ter	stop_gained	8/15	2		P2
PATL2	ENST00000558481.5 linkuse as main transcript	c.*213C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000572

AC:

AN:

1399384

Hom.:

Cov.:

AF XY:

0.00000869

AC XY:

AN XY:

690200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000649

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oocyte maturation defect 4

Pathogenic:2

Likely pathogenic, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	Apr 16, 2018	This variant is interpreted as a Likely Pathogenic, for Oocyte maturation defect 4, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PVS1-Strong => PVS1 downgraded in strength to Strong. -
Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 10, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.61

BayesDel_noAF

Pathogenic

0.63

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

MutationTaster

Benign

1.0

A;A;A

Vest4

0.51

GERP RS

4.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.32

Position offset: -24

DS_AL_spliceai

0.21

Position offset: 5

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