2-105361446-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001318895.3(FHL2):​c.689-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FHL2
NM_001318895.3 intron

Scores

2
Splicing: ADA: 0.00004112
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.861

Publications

0 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FHL2NM_001318895.3 linkc.689-12C>T intron_variant Intron 6 of 6 ENST00000530340.6 NP_001305824.1 Q14192-1Q6I9R8Q2XQU9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FHL2ENST00000530340.6 linkc.689-12C>T intron_variant Intron 6 of 6 1 NM_001318895.3 ENSP00000433567.2 Q14192-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456192
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
723940
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33254
American (AMR)
AF:
0.00
AC:
0
AN:
43858
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25932
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39578
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85338
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53342
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5730
European-Non Finnish (NFE)
AF:
9.02e-7
AC:
1
AN:
1108974
Other (OTH)
AF:
0.00
AC:
0
AN:
60186
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
12
DANN
Benign
0.74
PhyloP100
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000041
dbscSNV1_RF
Benign
0.046
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

Other links and lift over

dbSNP: rs2244182; hg19: chr2-105977903; API