Variant 14-75579262-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017791.3(FLVCR2):c.290G>A(p.Cys97Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FLVCR2
NM_017791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

Variant links:

Genes affected

FLVCR2 (HGNC:20105): (FLVCR choline and putative heme transporter 2) This gene encodes a member of the major facilitator superfamily. The encoded transmembrane protein is a calcium transporter. Unlike the related protein feline leukemia virus subgroup C receptor 1, the protein encoded by this locus does not bind to feline leukemia virus subgroup C envelope protein. The encoded protein may play a role in development of brain vascular endothelial cells, as mutations at this locus have been associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Aug 2010]

FLVCR2 links:

FLVCR2-AS1 (HGNC:55854): (FLVCR2 antisense RNA 1)

FLVCR2-AS1 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
FLVCR2	NM_017791.3 linkuse as main transcript	c.290G>A	p.Cys97Tyr	missense_variant	1/10	ENST00000238667.9
FLVCR2-AS1	NR_110552.1 linkuse as main transcript	n.327C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLVCR2	ENST00000238667.9 linkuse as main transcript	c.290G>A	p.Cys97Tyr	missense_variant	1/10	1	NM_017791.3	P1	Q9UPI3-1
FLVCR2-AS1	ENST00000455232.1 linkuse as main transcript	n.327C>T		non_coding_transcript_exon_variant	1/3	1
FLVCR2-AS1	ENST00000693551.1 linkuse as main transcript	n.391C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.290G>A (p.C97Y) alteration is located in exon 1 (coding exon 1) of the FLVCR2 gene. This alteration results from a G to A substitution at nucleotide position 290, causing the cysteine (C) at amino acid position 97 to be replaced by a tyrosine (Y). 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

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.31

Sift

Uncertain

0.015

Sift4G

Uncertain

0.016

Polyphen

0.87

Vest4

0.66

MutPred

0.56

Gain of catalytic residue at S95 (P = 0.0013);

MVP

0.71

MPC

1.1

ClinPred

0.99

GERP RS

5.9

Varity_R

0.90

gMVP

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over