chr2-105373716-G-A
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001318895.3(FHL2):c.174C>T(p.Asp58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00033 ( 0 hom. )
Consequence
FHL2
NM_001318895.3 synonymous
NM_001318895.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.26
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 2-105373716-G-A is Benign according to our data. Variant chr2-105373716-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 163492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-105373716-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=2.26 with no splicing effect.
BS2
High AC in GnomAd4 at 30 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FHL2 | NM_001318895.3 | c.174C>T | p.Asp58= | synonymous_variant | 4/7 | ENST00000530340.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FHL2 | ENST00000530340.6 | c.174C>T | p.Asp58= | synonymous_variant | 4/7 | 1 | NM_001318895.3 | P1 | |
ENST00000457290.2 | n.41-2152G>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000151 AC: 38AN: 251328Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135840
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GnomAD4 exome AF: 0.000335 AC: 489AN: 1461720Hom.: 0 Cov.: 31 AF XY: 0.000316 AC XY: 230AN XY: 727162
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GnomAD4 genome AF: 0.000197 AC: 30AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | Asp58Asp in exon 3 of FHL2: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue, is not located within th e splice consensus sequence. It has been identified in 3/7020 European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs141208906). Asp58Asp in exon 3 of FHL2 (rs 141208906; allele frequency = 3/7020) ** - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Aug 16, 2016 | - - |
Primary dilated cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at