Genetic Variant NM_030764.4:c.1486A>C (chr1-157746873-T-G) – 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_030764.4(FCRL2):c.1486A>C(p.Lys496Gln) variant causes a missense, splice region 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. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FCRL2
NM_030764.4 missense, splice_region

Scores

Splicing: ADA: 0.0001173

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.168

Publications

0 publications found

Variant links:

Genes affected

FCRL2 (HGNC:14875): (Fc receptor like 2) This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein has four extracellular C2-type immunoglobulin domains, a transmembrane domain and a cytoplasmic domain that contains one immunoreceptor-tyrosine activation motif and two immunoreceptor-tyrosine inhibitory motifs. This protein may be a prognostic marker for chronic lymphocytic leukemia. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Apr 2009]

FCRL2 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 (MetaRNN=0.066967785).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030764.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRL2	NM_030764.4	MANE Select	c.1486A>C	p.Lys496Gln	missense splice_region	Exon 11 of 12	NP_110391.2
FCRL2	NM_001159488.2		c.1308-99A>C		intron	N/A	NP_001152960.1	B4DVJ9
FCRL2	NR_125358.2		n.627A>C		splice_region non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRL2	ENST00000361516.8	TSL:1 MANE Select	c.1486A>C	p.Lys496Gln	missense splice_region	Exon 11 of 12	ENSP00000355157.3	Q96LA5-1
FCRL2	ENST00000368181.4	TSL:1	c.568A>C	p.Lys190Gln	missense splice_region	Exon 7 of 8	ENSP00000357163.4	Q96LA5-5
FCRL2	ENST00000368178.3	TSL:1	n.3404A>C		splice_region non_coding_transcript_exon	Exon 6 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.013

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.38

M_CAP

Benign

0.0025

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

-0.17

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.81

REVEL

Benign

0.017

Sift

Benign

0.063

Sift4G

Benign

0.20

Polyphen

0.24

Vest4

0.17

MutPred

0.40

Loss of ubiquitination at K496 (P = 0.0051)

MVP

0.17

MPC

0.041

ClinPred

0.15

GERP RS

1.1

Varity_R

0.088

gMVP

0.11

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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