chr15-44669096-C-T

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001387263.1(PATL2):c.1108G>A(p.Gly370Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000644 in 1,396,952 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

PATL2
NM_001387263.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 5.61

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

oocyte maturation defect 4
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

PATL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PATL2	NM_001387263.1 link	c.1108G>A	p.Gly370Arg	missense_variant	Exon 14 of 18	ENST00000682850.1	NP_001374192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PATL2	ENST00000682850.1 link	c.1108G>A	p.Gly370Arg	missense_variant	Exon 14 of 18		NM_001387263.1	ENSP00000508024.1	C9JE40
PATL2	ENST00000434130.6 link	c.1108G>A	p.Gly370Arg	missense_variant	Exon 12 of 16	5		ENSP00000416673.1	C9JE40
PATL2	ENST00000560780.1 link	c.541G>A	p.Gly181Arg	missense_variant	Exon 11 of 15	2		ENSP00000453695.1	H0YMQ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000660

AC:

AN:

151474

AF XY:

0.0000124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000644

AC:

AN:

1396952

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

688790

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31546

American (AMR)

AF:

0.00

AC:

AN:

35382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25014

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35694

South Asian (SAS)

AF:

0.00

AC:

AN:

78942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00000650

AC:

AN:

1077596

Other (OTH)

AF:

0.00

AC:

AN:

57888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oocyte maturation defect 4

Pathogenic:1Uncertain:1

Apr 16, 2018

SIB Swiss Institute of Bioinformatics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:curation

This variant is interpreted as a Uncertain Significance, 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. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease. -

Apr 10, 2023

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.41

T;T;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

.;T;T

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Uncertain

0.15

MutationAssessor

Uncertain

2.4

M;M;.

PhyloP100

5.6

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-7.2

D;D;D

REVEL

Pathogenic

0.77

Sift

Uncertain

0.024

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.92

P;P;.

Vest4

0.89

MutPred

0.84

Gain of MoRF binding (P = 0.0362);Gain of MoRF binding (P = 0.0362);.;

MVP

0.50

MPC

.;3.40522473235E-4;.

ClinPred

0.94

GERP RS

5.6

Varity_R

0.67

gMVP

0.85

Mutation Taster

=2/98

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over