1-157767428-T-C

Variant names:

• chr1-157767428-T-C
• rs376615407
• NM_030764.4:c.965A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030764.4(FCRL2):​c.965A>G​(p.Glu322Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FCRL2 NM_030764.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
FCRL2	NM_030764.4	c.965A>G	p.Glu322Gly	missense_variant	Exon 6 of 12	ENST00000361516.8	NP_110391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL2	ENST00000361516.8	c.965A>G	p.Glu322Gly	missense_variant	Exon 6 of 12	1	NM_030764.4	ENSP00000355157.3
FCRL2	ENST00000469986.1	c.206A>G	p.Glu69Gly	missense_variant	Exon 1 of 2	1		ENSP00000417393.1
FCRL2	ENST00000368181.4	c.311-457A>G		intron_variant	Intron 3 of 7	1		ENSP00000357163.4
FCRL2	ENST00000368178.3	n.2883A>G		non_coding_transcript_exon_variant	Exon 1 of 7	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.965A>G (p.E322G) alteration is located in exon 6 (coding exon 6) of the FCRL2 gene. This alteration results from a A to G substitution at nucleotide position 965, causing the glutamic acid (E) at amino acid position 322 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T;.
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.32
MutPred		0.66		Gain of catalytic residue at A323 (P = 0.121);.;
MVP		0.37
MPC		0.28
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.50
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs376615407; hg19: chr1-157737218;