15-44668999-C-T

Variant names:

• chr15-44668999-C-T
• rs199627539
• NM_001387263.1:c.1205G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001387263.1(PATL2):​c.1205G>A​(p.Arg402Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,548,254 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000050 (1 hom.)
• Consequence: PATL2 NM_001387263.1 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.249
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042292953).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387263.1. 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.1205G>A	p.Arg402Gln	missense	Exon 14 of 18	NP_001374192.1	C9JE40
	PATL2	NM_001145112.2		c.1205G>A	p.Arg402Gln	missense	Exon 12 of 16	NP_001138584.1	C9JE40
	PATL2	NM_001387261.1		c.1205G>A	p.Arg402Gln	missense	Exon 12 of 16	NP_001374190.1	C9JE40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATL2	ENST00000682850.1	MANE Select	c.1205G>A	p.Arg402Gln	missense	Exon 14 of 18	ENSP00000508024.1	C9JE40
	PATL2	ENST00000434130.6	TSL:5	c.1205G>A	p.Arg402Gln	missense	Exon 12 of 16	ENSP00000416673.1	C9JE40
	PATL2	ENST00000890223.1		c.1205G>A	p.Arg402Gln	missense	Exon 13 of 17	ENSP00000560282.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000106 AC: 16 AN: 151264 AF XY: 0.0000873

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000452

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000514

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000501 AC: 70 AN: 1395970 Hom.: 1 Cov.: 32 AF XY: 0.0000465 AC XY: 32 AN XY: 688256

African (AFR) AF: 0.00 AC: 0 AN: 31548

American (AMR) AF: 0.000340 AC: 12 AN: 35344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24898

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35702

South Asian (SAS) AF: 0.000152 AC: 12 AN: 78784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.0000418 AC: 45 AN: 1076992

Other (OTH) AF: 0.00 AC: 0 AN: 57852

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.000131 AC: 2 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000478 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000825 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.25
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.033
Sift	Benign	0.19	T
Sift4G	Benign	0.26	T
Polyphen		0.28	B
Vest4		0.065
MutPred		0.48		Loss of helix (P = 0.2022)
MVP		0.076
MPC		0.00034
ClinPred		0.038	T
GERP RS		-0.88
Varity_R		0.041
gMVP		0.13
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs199627539; hg19: chr15-44961197; COSMIC: COSV101436313; COSMIC: COSV101436313;