NM_030764.4:c.1019C>G

Variant names:

• chr1-157767374-G-C
• NM_030764.4:c.1019C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030764.4(FCRL2):​c.1019C>G​(p.Thr340Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. 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: -1.18
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13807458).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL2	NM_030764.4	MANE Select	c.1019C>G	p.Thr340Ser	missense	Exon 6 of 12	NP_110391.2
	FCRL2	NM_001159488.2		c.1019C>G	p.Thr340Ser	missense	Exon 6 of 9	NP_001152960.1	B4DVJ9
	FCRL2	NR_125358.2		n.370-403C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL2	ENST00000361516.8	TSL:1 MANE Select	c.1019C>G	p.Thr340Ser	missense	Exon 6 of 12	ENSP00000355157.3	Q96LA5-1
	FCRL2	ENST00000469986.1	TSL:1	c.260C>G	p.Thr87Ser	missense	Exon 1 of 2	ENSP00000417393.1	Q96LA5-3
	FCRL2	ENST00000368181.4	TSL:1	c.311-403C>G		intron	N/A	ENSP00000357163.4	Q96LA5-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.067
DANN	Benign	0.66
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.024
Sift	Benign	0.30	T
Sift4G	Benign	0.23	T
Polyphen		0.24	B
Vest4		0.16
MutPred		0.27		Gain of disorder (P = 0.0293)
MVP		0.12
MPC		0.098
ClinPred		0.29	T
GERP RS		-2.7
PromoterAI		-0.0034	Neutral
Varity_R		0.049
gMVP		0.070
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr1-157737164;