Genetic Variant B2M:p.Ser14Phe (chr15-44711587-C-T) – 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_004048.4(B2M):c.41C>T(p.Ser14Phe) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S14C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

B2M
NM_004048.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.841

Publications

0 publications found

Variant links:

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]

B2M links:

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)

PATL2 links:

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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 (MetaRNN=0.05172482).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004048.4. 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
	B2M	NM_004048.4	MANE Select	c.41C>T	p.Ser14Phe	missense	Exon 1 of 4	NP_004039.1	P61769
	PATL2	NM_001387260.1		c.-331G>A		upstream_gene	N/A	NP_001374189.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B2M	ENST00000648006.3	MANE Select	c.41C>T	p.Ser14Phe	missense	Exon 1 of 4	ENSP00000497910.1	P61769
B2M	ENST00000559916.1	TSL:1	c.41C>T	p.Ser14Phe	missense	Exon 1 of 3	ENSP00000453350.1	P61769
B2M	ENST00000557901.5	TSL:1	n.41C>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000452861.1	Q16446

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.92

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.017

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.085

M_CAP

Benign

0.0036

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.9

PhyloP100

-0.84

PrimateAI

Benign

0.36

PROVEAN

Benign

0.19

REVEL

Benign

0.013

Sift

Benign

0.67

Sift4G

Benign

0.73

Polyphen

0.0010

Vest4

0.20

MutPred

0.50

Gain of helix (P = 0.0143)

MVP

0.29

MPC

1.1

ClinPred

0.13

GERP RS

-3.7

PromoterAI

-0.059

Neutral

(source)

Varity_R

0.051

gMVP

0.54

Mutation Taster

=88/12

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over