rs769888361

Variant summary

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

The NM_001318895.3(FHL2):ā€‹c.739G>Cā€‹(p.Asp247His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

FHL2
NM_001318895.3 missense

Scores

1
14
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.12
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FHL2NM_001318895.3 linkc.739G>C p.Asp247His 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.739G>C p.Asp247His missense_variant Exon 7 of 7 1 NM_001318895.3 ENSP00000433567.2 Q14192-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
249856
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135198
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461694
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727166
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Uncertain
0.066
T
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.73
.;.;D;D;D;D;D
Eigen
Benign
-0.0035
Eigen_PC
Benign
0.044
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.88
.;.;.;.;.;.;D
M_CAP
Uncertain
0.16
D
MetaRNN
Uncertain
0.63
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.19
D
MutationAssessor
Uncertain
2.2
.;.;M;M;M;M;M
PrimateAI
Pathogenic
0.85
D
PROVEAN
Uncertain
-4.2
.;D;D;D;D;D;D
REVEL
Uncertain
0.61
Sift
Uncertain
0.027
.;D;T;T;T;T;T
Sift4G
Benign
0.49
T;T;T;T;T;T;T
Polyphen
0.12
.;.;B;B;B;B;B
Vest4
0.62
MutPred
0.46
.;.;Gain of methylation at K252 (P = 0.1134);Gain of methylation at K252 (P = 0.1134);Gain of methylation at K252 (P = 0.1134);Gain of methylation at K252 (P = 0.1134);Gain of methylation at K252 (P = 0.1134);
MVP
0.98
ClinPred
0.95
D
GERP RS
2.7
Varity_R
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs769888361; hg19: chr2-105977841; API