15-44711166-T-G

Variant names:

• chr15-44711166-T-G
• rs2255235
• NM_001387263.1:c.-400A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387263.1(PATL2):​c.-400A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 410,114 control chromosomes in the GnomAD database, including 148,442 homozygotes. 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 0.82 (51567 hom., cov: 30)
  • Exomes 𝑓: 0.86 (96875 hom.)
• Consequence: PATL2 NM_001387263.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 16 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]

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATL2	NM_001387263.1	MANE Select	c.-400A>C		5_prime_UTR	Exon 1 of 18	NP_001374192.1
	PATL2	NM_001387261.1		c.-222A>C		5_prime_UTR	Exon 1 of 16	NP_001374190.1
	PATL2	NM_001387262.1		c.-490A>C		5_prime_UTR	Exon 1 of 17	NP_001374191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATL2	ENST00000682850.1	MANE Select	c.-400A>C		5_prime_UTR	Exon 1 of 18	ENSP00000508024.1
	PATL2	ENST00000558573.1	TSL:2	n.151A>C		non_coding_transcript_exon	Exon 1 of 2
	B2M	ENST00000695792.1		n.-192T>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124166 AN: 151940 Hom.: 51539 Cov.: 30

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.835

GnomAD4 exome AF: 0.864 AC: 222927 AN: 258056 Hom.: 96875 Cov.: 0 AF XY: 0.859 AC XY: 117012 AN XY: 136170

African (AFR) AF: 0.654 AC: 5363 AN: 8204

American (AMR) AF: 0.887 AC: 10870 AN: 12260

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 6569 AN: 7794

East Asian (EAS) AF: 0.872 AC: 12828 AN: 14712

South Asian (SAS) AF: 0.802 AC: 29219 AN: 36428

European-Finnish (FIN) AF: 0.867 AC: 11108 AN: 12808

Middle Eastern (MID) AF: 0.881 AC: 966 AN: 1096

European-Non Finnish (NFE) AF: 0.889 AC: 133463 AN: 150060

Other (OTH) AF: 0.853 AC: 12541 AN: 14694

GnomAD4 genome AF: 0.817 AC: 124241 AN: 152058 Hom.: 51567 Cov.: 30 AF XY: 0.817 AC XY: 60711 AN XY: 74294

African (AFR) AF: 0.657 AC: 27219 AN: 41426

American (AMR) AF: 0.881 AC: 13456 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2942 AN: 3470

East Asian (EAS) AF: 0.842 AC: 4353 AN: 5172

South Asian (SAS) AF: 0.785 AC: 3777 AN: 4810

European-Finnish (FIN) AF: 0.868 AC: 9176 AN: 10574

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60466 AN: 68014

Other (OTH) AF: 0.832 AC: 1751 AN: 2104

Alfa AF: 0.872 Hom.: 126051

Bravo AF: 0.811

Asia WGS AF: 0.745 AC: 2592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.9
DANN	Benign	0.69
PhyloP100		-1.1
PromoterAI		0.0070	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2255235; hg19: chr15-45003364; COSMIC: COSV62564956;