2-218982039-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017521.3(FEV):​c.345C>G​(p.Ser115Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

FEV
NM_017521.3 missense

Scores

5
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03
Variant links:
Genes affected
FEV (HGNC:18562): (FEV transcription factor, ETS family member) This gene belongs to the ETS transcription factor family. ETS family members have a highly conserved 85-amino acid ETS domain that binds purine-rich DNA sequences. The alanine-rich C-terminus of this gene indicates that it may act as a transcription repressor. This gene is exclusively expressed in neurons of the central serotonin (5-HT) system, a system implicated in the pathogeny of such psychiatric diseases as depression, anxiety, and eating disorders. In some types of Ewing tumors, this gene is fused to the Ewing sarcoma (EWS) gene following chromosome translocations. [provided by RefSeq, Jul 2008]
LINC00608 (HGNC:27179): (long intergenic non-protein coding RNA 608)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36773756).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FEVNM_017521.3 linkc.345C>G p.Ser115Arg missense_variant 3/3 ENST00000295727.2 NP_059991.1 Q99581
FEVXM_047444822.1 linkc.60C>G p.Ser20Arg missense_variant 3/3 XP_047300778.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FEVENST00000295727.2 linkc.345C>G p.Ser115Arg missense_variant 3/31 NM_017521.3 ENSP00000295727.1 Q99581
FEVENST00000470119.1 linkn.463C>G non_coding_transcript_exon_variant 2/22
LINC00608ENST00000627043.2 linkn.1201+2659G>C intron_variant 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 17, 2024The c.345C>G (p.S115R) alteration is located in exon 3 (coding exon 3) of the FEV gene. This alteration results from a C to G substitution at nucleotide position 345, causing the serine (S) at amino acid position 115 to be replaced by an arginine (R). 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
0.98
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.41
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.37
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.050
N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.18
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.80
P
Vest4
0.32
MutPred
0.33
Gain of solvent accessibility (P = 0.0739);
MVP
0.11
ClinPred
0.91
D
GERP RS
2.6
Varity_R
0.88
gMVP
0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219846761; API