rs750884671

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_001318895.3(FHL2):ā€‹c.760T>Gā€‹(p.Cys254Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

FHL2
NM_001318895.3 missense

Scores

16
2
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.27
Variant links:
Genes affected
FHL2 (HGNC:3703): (four and a half LIM domains 2) This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. This protein is thought to have a role in the assembly of extracellular membranes. Also, this gene is down-regulated during transformation of normal myoblasts to rhabdomyosarcoma cells and the encoded protein may function as a link between presenilin-2 and an intracellular signaling pathway. Multiple alternatively spliced variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2016]
C2orf49 (HGNC:28772): (chromosome 2 open reading frame 49) Predicted to be involved in embryonic morphogenesis. Located in nucleus. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.956
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FHL2NM_001318895.3 linkc.760T>G p.Cys254Gly missense_variant Exon 7 of 7 ENST00000530340.6 NP_001305824.1 Q14192-1Q6I9R8Q2XQU9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FHL2ENST00000530340.6 linkc.760T>G p.Cys254Gly missense_variant Exon 7 of 7 1 NM_001318895.3 ENSP00000433567.2 Q14192-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250418
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135492
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461802
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727210
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:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.60
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.93
.;.;D;D;D;D;D
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.98
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
1.0
.;.;.;.;.;.;D
M_CAP
Pathogenic
0.73
D
MetaRNN
Pathogenic
0.96
D;D;D;D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
4.5
.;.;H;H;H;H;H
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-11
.;D;D;D;D;D;D
REVEL
Pathogenic
0.99
Sift
Pathogenic
0.0
.;D;D;D;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;D;D;D;D
Vest4
0.94
MutPred
0.76
.;.;Loss of methylation at K253 (P = 0.0298);Loss of methylation at K253 (P = 0.0298);Loss of methylation at K253 (P = 0.0298);Loss of methylation at K253 (P = 0.0298);Loss of methylation at K253 (P = 0.0298);
MVP
1.0
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.96

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.

Other links and lift over

dbSNP: rs750884671; hg19: chr2-105977820; API