14-75624639-CC-GT

Variant names:

• chr14-75624639-CC-GT
• NM_017791.3:c.839_840delCCinsGT
• FLVCR2 p.Pro280Arg

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PS1 PP3

The NM_017791.3(FLVCR2):​c.839_840delCCinsGT​(p.Pro280Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P280A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FLVCR2 NM_017791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.75
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Fowler syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PS1: Transcript NM_017791.3 (FLVCR2) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017791.3. 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
	FLVCR2	NM_017791.3	MANE Select	c.839_840delCCinsGT	p.Pro280Arg	missense	N/A	NP_060261.2	Q9UPI3-1
	FLVCR2	NM_001195283.2		c.224_225delCCinsGT	p.Pro75Arg	missense	N/A	NP_001182212.1	Q9UPI3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLVCR2	ENST00000238667.9	TSL:1 MANE Select	c.839_840delCCinsGT	p.Pro280Arg	missense	N/A	ENSP00000238667.4	Q9UPI3-1
	FLVCR2	ENST00000852195.1		c.839_840delCCinsGT	p.Pro280Arg	missense	N/A	ENSP00000522253.1
	FLVCR2	ENST00000943497.1		c.839_840delCCinsGT	p.Pro280Arg	missense	N/A	ENSP00000613556.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-76090982;