rs115841332
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001318895.3(FHL2):c.689-10C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,610,242 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0041 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 6 hom. )
Consequence
FHL2
NM_001318895.3 splice_polypyrimidine_tract, intron
NM_001318895.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0005799
2
Clinical Significance
Conservation
PhyloP100: 0.394
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 2-105361444-G-C is Benign according to our data. Variant chr2-105361444-G-C is described in ClinVar as [Benign]. Clinvar id is 48328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-105361444-G-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000449 (655/1457918) while in subpopulation AFR AF= 0.0166 (554/33324). AF 95% confidence interval is 0.0155. There are 6 homozygotes in gnomad4_exome. There are 269 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 632 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FHL2 | NM_001318895.3 | c.689-10C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000530340.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FHL2 | ENST00000530340.6 | c.689-10C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001318895.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00415 AC: 632AN: 152206Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00112 AC: 275AN: 245218Hom.: 1 AF XY: 0.000837 AC XY: 111AN XY: 132606
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GnomAD4 exome AF: 0.000449 AC: 655AN: 1457918Hom.: 6 Cov.: 31 AF XY: 0.000371 AC XY: 269AN XY: 724932
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GnomAD4 genome ? AF: 0.00415 AC: 632AN: 152324Hom.: 6 Cov.: 32 AF XY: 0.00381 AC XY: 284AN XY: 74492
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 16, 2012 | 689-10C>G in intron 5 of FHL2: This variant is not expected to have clinical sig nificance because it is not located within the splice consensus sequence and has been identified in 1.3% (52/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/E VS; dbSNP rs115841332). - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jun 14, 2016 | - - |
Primary dilated cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at