rs2244182
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001318895.3(FHL2):c.689-12C>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 0.162 in 1,606,806 control chromosomes in the GnomAD database, including 27,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.21 ( 4349 hom., cov: 33)
Exomes 𝑓: 0.16 ( 22707 hom. )
Consequence
FHL2
NM_001318895.3 splice_polypyrimidine_tract, intron
NM_001318895.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0005900
2
Clinical Significance
Conservation
PhyloP100: 0.861
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=-0.67).
BP6
Variant 2-105361446-G-C is Benign according to our data. Variant chr2-105361446-G-C is described in ClinVar as [Benign]. Clinvar id is 48329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-105361446-G-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FHL2 | NM_001318895.3 | c.689-12C>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.689-12C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001318895.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.213 AC: 32315AN: 152008Hom.: 4347 Cov.: 33
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GnomAD3 exomes AF: 0.210 AC: 51251AN: 244478Hom.: 7401 AF XY: 0.199 AC XY: 26372AN XY: 132202
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GnomAD4 exome AF: 0.157 AC: 228479AN: 1454680Hom.: 22707 Cov.: 31 AF XY: 0.156 AC XY: 113016AN XY: 723240
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GnomAD4 genome AF: 0.213 AC: 32349AN: 152126Hom.: 4349 Cov.: 33 AF XY: 0.215 AC XY: 15996AN XY: 74378
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 13, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 16, 2012 | 689-12C>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 33% (1242/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS; dbSNP rs2244182). - |
Primary dilated cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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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