rs2278502

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001318895.3(FHL2):c.688+12G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,611,904 control chromosomes in the GnomAD database, including 111,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7902 hom., cov: 32)

Exomes 𝑓: 0.37 ( 103863 hom. )

Consequence

FHL2
NM_001318895.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.336

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]

FHL2 links:

ENSG00000238273 (HGNC:):

ENSG00000238273 links:

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]

C2orf49 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-105363273-C-A is Benign according to our data. Variant chr2-105363273-C-A is described in ClinVar as [Benign]. Clinvar id is 48327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-105363273-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHL2	NM_001318895.3 link	c.688+12G>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
FHL2	ENST00000530340.6 link	c.688+12G>T		intron_variant	Intron 6 of 6	1	NM_001318895.3	ENSP00000433567.2		Q14192-1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47312

AN:

151946

Hom.:

7902

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.309

GnomAD3 exomes

AF:

0.332

AC:

82844

AN:

249662

Hom.:

14381

AF XY:

0.341

AC XY:

45939

AN XY:

134878

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.323

Gnomad EAS exome

AF:

0.187

Gnomad SAS exome

AF:

0.373

Gnomad FIN exome

AF:

0.377

Gnomad NFE exome

AF:

0.380

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.372

AC:

543657

AN:

1459840

Hom.:

103863

Cov.:

AF XY:

0.373

AC XY:

271137

AN XY:

726022

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.374

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.311

AC:

47327

AN:

152064

Hom.:

7902

Cov.:

AF XY:

0.309

AC XY:

22989

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.311

Gnomad4 ASJ

AF:

0.318

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.365

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.308

Alfa

AF:

0.311

Hom.:

2205

Bravo

AF:

0.298

Asia WGS

AF:

0.298

AC:

1036

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 16, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jul 30, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary dilated cardiomyopathy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.082

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over