15-44711166-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387263.1(PATL2):​c.-400A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: 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=-0.79).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 258394 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 136348

African (AFR) AF: 0.00 AC: 0 AN: 8224

American (AMR) AF: 0.00 AC: 0 AN: 12272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7808

East Asian (EAS) AF: 0.00 AC: 0 AN: 14724

South Asian (SAS) AF: 0.00 AC: 0 AN: 36484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1098

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 150230

Other (OTH) AF: 0.00 AC: 0 AN: 14724

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.69
PhyloP100		-1.1
PromoterAI		0.0096	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;