rs13908

chr11-72218687-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000803.5(FOLR2):c.103A>G(p.Lys35Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOLR2 NM_000803.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.68

Genes affected

FOLR2 (HGNC:3793): (folate receptor beta) The protein encoded by this gene is a member of the folate receptor (FOLR) family, and these genes exist in a cluster on chromosome 11. Members of this gene family have a high affinity for folic acid and for several reduced folic acid derivatives, and they mediate delivery of 5-methyltetrahydrofolate to the interior of cells. This protein has a 68% and 79% sequence homology with the FOLR1 and FOLR3 proteins, respectively. Although this protein was originally thought to be specific to placenta, it can also exist in other tissues, and it may play a role in the transport of methotrexate in synovial macrophages in rheumatoid arthritis patients. Multiple transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOLR2	NM_000803.5	c.103A>G	p.Lys35Glu	missense_variant	2/5	ENST00000298223.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOLR2	ENST00000298223.11	c.103A>G	p.Lys35Glu	missense_variant	2/5	1	NM_000803.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
Cadd	Uncertain	25
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.22	T;T;.;T;T;.;T;T;.
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;T;D;D;D;D;D;D;D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.26	D
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.2	D;D;.;D;D;D;D;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0030	D;D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D;D;D;D
Polyphen		0.99	.;D;.;.;.;.;.;.;.
Vest4		0.53
MutPred		0.71		.;Loss of methylation at K35 (P = 0.0062);.;.;.;.;Loss of methylation at K35 (P = 0.0062);.;Loss of methylation at K35 (P = 0.0062);
MVP		0.89
MPC		0.26
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.88
gMVP		0.72

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: rs13908; hg19: chr11-71929731;