rs1351320025

Positions:

• chr15-44669869-G-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_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
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 6.46

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]

ACMG classification

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	c.784C>T	p.Arg262Ter	stop_gained	11/18	ENST00000682850.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000572 AC: 8 AN: 1399384 Hom.: 0 Cov.: 31 AF XY: 0.00000869 AC XY: 6 AN XY: 690200

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.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

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	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
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

Other links and lift over

dbSNP: rs1351320025; hg19: chr15-44962067; COSMIC: COSV71384680; COSMIC: COSV71384680;