chr15-44672425-G-A

Variant names:

• chr15-44672425-G-A
• rs548527219
• NM_001387263.1:c.478C>T

Variant summary

Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PS3 PM2 PP3_Moderate PP5_Very_Strong

The NM_001330283.2(PATL2):​c.-173C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,551,570 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 (★★). ClinVar reports functional evidence for this variant: "SCV000787499: PS3 downgraded in strength to Moderate (PMID:28965844).".

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: PATL2 NM_001330283.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely pathogenic criteria provided, multiple submitters, no conflicts P:4
• Conservation: PhyloP100: 1.07
• Publications: 7 publications found

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)

ACMG classification

Our verdict: Pathogenic. The variant received 16 ACMG points.

• PS3: PS3 evidence extracted from ClinVar submissions: SCV000787499: PS3 downgraded in strength to Moderate (PMID:28965844).
• PM2: Very rare variant in population databases, with high coverage
• PP3: BayesDel_addAF computational evidence supports a deleterious effect, 0.362
• PP5: Variant 15-44672425-G-A is Pathogenic according to our data. Variant chr15-44672425-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 444045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330283.2. 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
	PATL2	NM_001387263.1	MANE Select	c.478C>T	p.Arg160*	stop_gained	Exon 8 of 18	NP_001374192.1	C9JE40
	PATL2	NM_001330283.2		c.-173C>T		5_prime_UTR_premature_start_codon_gain	Exon 5 of 15	NP_001317212.1	H0YMQ2
	PATL2	NM_001145112.2		c.478C>T	p.Arg160*	stop_gained	Exon 6 of 16	NP_001138584.1	C9JE40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATL2	ENST00000682850.1	MANE Select	c.478C>T	p.Arg160*	stop_gained	Exon 8 of 18	ENSP00000508024.1	C9JE40
	PATL2	ENST00000560780.1	TSL:2	c.-173C>T		5_prime_UTR_premature_start_codon_gain	Exon 5 of 15	ENSP00000453695.1	H0YMQ2
	PATL2	ENST00000434130.6	TSL:5	c.478C>T	p.Arg160*	stop_gained	Exon 6 of 16	ENSP00000416673.1	C9JE40

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000324 AC: 5 AN: 154084 AF XY: 0.0000245

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000917

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000503

Gnomad OTH exome AF: 0.000231

GnomAD4 exome AF: 0.0000286 AC: 40 AN: 1399404 Hom.: 0 Cov.: 31 AF XY: 0.0000304 AC XY: 21 AN XY: 690210

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.0000840 AC: 3 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49278

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5698

European-Non Finnish (NFE) AF: 0.0000260 AC: 28 AN: 1078966

Other (OTH) AF: 0.0000862 AC: 5 AN: 58006

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000559 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
3	-	-	Oocyte maturation defect 4 (3)
1	-	-	Oocyte maturation defect 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.49
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.78	D
PhyloP100		1.1
Vest4		0.41
GERP RS		1.6
Mutation Taster		=4/196	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs548527219; hg19: chr15-44964623; COSMIC: COSV71384273; COSMIC: COSV71384273;