2-105361319-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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. Variant chr2-105361319-G-A is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.0936

AC:

23481

AN:

250918

Hom.:

1246

AF XY:

0.0934

AC XY:

12675

AN XY:

135668

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 SAS exome

AF:

0.0552

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

Gnomad4 AFR exome

AF:

0.0230

Gnomad4 AMR exome

AF:

0.100

Gnomad4 ASJ exome

AF:

0.0896

Gnomad4 EAS exome

AF:

0.0207

Gnomad4 SAS exome

AF:

0.0548

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.0866

AC:

13179

AN:

152234

Hom.:

710

Cov.:

AF XY:

0.0849

AC XY:

6318

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0257

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.0927

Gnomad4 EAS

AF:

0.0232

Gnomad4 SAS

AF:

0.0516

Gnomad4 FIN

AF:

0.0995

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.0929

Alfa

AF:

0.111

Hom.:

1286

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

DANN

Benign

0.42

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