rs863225287

Variant names:

• chr15-44711614-G-A
• rs863225287
• NM_004048.4:c.67+1G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-44711614-G-A
• chr15-44711614-G-C
• chr15-44711614-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004048.4(B2M):​c.67+1G>A variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: B2M NM_004048.4 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: - - O:1
• Conservation: PhyloP100: 4.68
• Publications: 0 publications found

Genes affected

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]

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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B2M	NM_004048.4	c.67+1G>A		splice_donor_variant, intron_variant	Intron 1 of 3	ENST00000648006.3	NP_004039.1
B2M	XM_005254549.4	c.67+1G>A		splice_donor_variant, intron_variant	Intron 1 of 1		XP_005254606.1
PATL2	NM_001387260.1	c.-358C>T		upstream_gene_variant			NP_001374189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B2M	ENST00000648006.3	c.67+1G>A		splice_donor_variant, intron_variant	Intron 1 of 3		NM_004048.4	ENSP00000497910.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: -

Submissions summary: Other:1

Revision: -

Submissions by phenotype

not provided Other:1

-

MutSpliceDB: a database of splice sites variants effects on splicing, NIH

Significance: not provided

Review Status: no classification provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.97	D
PhyloP100		4.7
GERP RS		5.3
PromoterAI		-0.24	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.92
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.97		Position offset: -1

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

Other links and lift over

dbSNP: rs863225287; hg19: chr15-45003812; COSMIC: COSV62562857; COSMIC: COSV62562857;