dbSNP rs2255235: PATL2:c.-400A>T (chr15-44711166-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001387263.1(PATL2):c.-400A>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 0.0000122 in 410,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PATL2
NM_001387263.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

16 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 links:

B2M (HGNC:914): (beta-2-microglobulin) This gene encodes a serum protein found in association with the major histocompatibility complex (MHC) class I heavy chain on the surface of nearly all nucleated cells. The protein has a predominantly beta-pleated sheet structure that can form amyloid fibrils in some pathological conditions. The encoded antimicrobial protein displays antibacterial activity in amniotic fluid. A mutation in this gene has been shown to result in hypercatabolic hypoproteinemia.[provided by RefSeq, Aug 2014]

B2M Gene-Disease associations (from GenCC):

hypoproteinemia, hypercatabolic
Inheritance: AR Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
variant ABeta2M amyloidosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
MHC class I deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
familial visceral amyloidosis
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

B2M links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PATL2	NM_001387263.1 link	c.-400A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 18	ENST00000682850.1	NP_001374192.1
PATL2	NM_001387263.1 link	c.-400A>T		5_prime_UTR_variant	Exon 1 of 18	ENST00000682850.1	NP_001374192.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PATL2	ENST00000682850.1 link	c.-400A>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 18		NM_001387263.1	ENSP00000508024.1	C9JE40
PATL2	ENST00000682850.1 link	c.-400A>T	5_prime_UTR_variant	Exon 1 of 18		NM_001387263.1	ENSP00000508024.1	C9JE40
PATL2	ENST00000558573.1 link	n.151A>T	non_coding_transcript_exon_variant	Exon 1 of 2	2
B2M	ENST00000695792.1 link	n.-192T>A	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

258394

Hom.:

Cov.:

AF XY:

0.00000733

AC XY:

AN XY:

136348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8224

American (AMR)

AF:

0.00

AC:

AN:

12272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7808

East Asian (EAS)

AF:

0.00

AC:

AN:

14724

South Asian (SAS)

AF:

0.00

AC:

AN:

36484

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1098

European-Non Finnish (NFE)

AF:

0.00000666

AC:

AN:

150230

Other (OTH)

AF:

0.000136

AC:

AN:

14724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151976

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41330

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

126051

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.5

(source)

DANN

Benign

0.75

PhyloP100

-1.1

PromoterAI

0.0022

Neutral

(source)

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over