rs3087523

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001318895.3(FHL2):c.804C>T(p.Asp268Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,613,654 control chromosomes in the GnomAD database, including 10,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 710 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9657 hom. )

Consequence

FHL2
NM_001318895.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.653

Publications

20 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]

FHL2 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 was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 2-105361319-G-A is Benign according to our data. Variant chr2-105361319-G-A is described in ClinVar as [Benign]. Clinvar id is 48331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.653 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHL2	NM_001318895.3 link	c.804C>T	p.Asp268Asp	synonymous_variant	Exon 7 of 7	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.804C>T	p.Asp268Asp	synonymous_variant	Exon 7 of 7	1	NM_001318895.3	ENSP00000433567.2		Q14192-1

Frequencies

GnomAD3 genomes

AF:

0.0866

AC:

13176

AN:

152116

Hom.:

710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0257

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.0927

Gnomad EAS

AF:

0.0231

Gnomad SAS

AF:

0.0509

Gnomad FIN

AF:

0.0995

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.0939

GnomAD2 exomes

AF:

0.0936

AC:

23481

AN:

250918

AF XY:

0.0934

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.0998

Gnomad ASJ exome

AF:

0.0901

Gnomad EAS exome

AF:

0.0253

Gnomad FIN exome

AF:

0.0975

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.111

AC:

161934

AN:

1461420

Hom.:

9657

Cov.:

AF XY:

0.109

AC XY:

79500

AN XY:

727036

show subpopulations

African (AFR)

AF:

0.0230

AC:

770

AN:

33474

American (AMR)

AF:

0.100

AC:

4480

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

2341

AN:

26128

East Asian (EAS)

AF:

0.0207

AC:

822

AN:

39688

South Asian (SAS)

AF:

0.0548

AC:

4727

AN:

86220

European-Finnish (FIN)

AF:

0.101

AC:

5405

AN:

53418

Middle Eastern (MID)

AF:

0.0882

AC:

509

AN:

5768

European-Non Finnish (NFE)

AF:

0.123

AC:

136704

AN:

1111634

Other (OTH)

AF:

0.102

AC:

6176

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6470

12939

19409

25878

32348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0866

AC:

13179

AN:

152234

Hom.:

710

Cov.:

AF XY:

0.0849

AC XY:

6318

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0257

AC:

1067

AN:

41542

American (AMR)

AF:

0.108

AC:

1646

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0927

AC:

322

AN:

3472

East Asian (EAS)

AF:

0.0232

AC:

120

AN:

5182

South Asian (SAS)

AF:

0.0516

AC:

248

AN:

4806

European-Finnish (FIN)

AF:

0.0995

AC:

1055

AN:

10604

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8492

AN:

68016

Other (OTH)

AF:

0.0929

AC:

196

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

643

1286

1928

2571

3214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.109

Hom.:

1562

Bravo

AF:

0.0849

Asia WGS

AF:

0.0320

AC:

110

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

- -

Mar 16, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Asp268Asp in exon 6 of FHL2: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue, is not located within t he splice consensus sequence, and has been identified in 12% (868/7020) of Europ ean American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS; dbSNP rs3087523). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Sep 06, 2018

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

-0.58

CADD

Benign

0.21

(source)

DANN

Benign

0.42

PhyloP100

-0.65

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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rs3087523

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over