2-105361304-G-A

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.819C>T(p.Pro273Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,040 control chromosomes in the GnomAD database, including 27,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2145 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25714 hom. )

Consequence

FHL2
NM_001318895.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.19

Publications

16 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=-0.73).

BP6

Variant 2-105361304-G-A is Benign according to our data. Variant chr2-105361304-G-A is described in ClinVar as [Benign]. Clinvar id is 48332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHL2	NM_001318895.3 link	c.819C>T	p.Pro273Pro	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.819C>T	p.Pro273Pro	synonymous_variant	Exon 7 of 7	1	NM_001318895.3	ENSP00000433567.2		Q14192-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24171

AN:

152098

Hom.:

2147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.0250

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.167

GnomAD2 exomes

AF:

0.158

AC:

39675

AN:

250382

AF XY:

0.162

show subpopulations

Gnomad AFR exome

AF:

0.0995

Gnomad AMR exome

AF:

0.0914

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.0253

Gnomad FIN exome

AF:

0.247

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.182

AC:

266232

AN:

1460824

Hom.:

25714

Cov.:

AF XY:

0.182

AC XY:

132086

AN XY:

726712

show subpopulations

African (AFR)

AF:

0.0978

AC:

3271

AN:

33438

American (AMR)

AF:

0.0962

AC:

4293

AN:

44608

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

5659

AN:

26116

East Asian (EAS)

AF:

0.0213

AC:

847

AN:

39678

South Asian (SAS)

AF:

0.129

AC:

11126

AN:

86086

European-Finnish (FIN)

AF:

0.243

AC:

13002

AN:

53416

Middle Eastern (MID)

AF:

0.196

AC:

1132

AN:

5764

European-Non Finnish (NFE)

AF:

0.195

AC:

216296

AN:

1111378

Other (OTH)

AF:

0.176

AC:

10606

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

10367

20735

31102

41470

51837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.159

AC:

24170

AN:

152216

Hom.:

2145

Cov.:

AF XY:

0.160

AC XY:

11901

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.102

AC:

4220

AN:

41542

American (AMR)

AF:

0.139

AC:

2121

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

748

AN:

3470

East Asian (EAS)

AF:

0.0253

AC:

131

AN:

5188

South Asian (SAS)

AF:

0.120

AC:

578

AN:

4824

European-Finnish (FIN)

AF:

0.251

AC:

2655

AN:

10580

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.192

AC:

13078

AN:

67994

Other (OTH)

AF:

0.165

AC:

349

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1029

2058

3086

4115

5144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.180

Hom.:

1722

Bravo

AF:

0.149

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

EpiCase

AF:

0.202

EpiControl

AF:

0.200

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Sep 16, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as benign because it does not change the amino acid a nd is frequent in the general population (rs11124029, MAF >1%). -

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

-0.73

CADD

Benign

0.41

(source)

DANN

Benign

0.61

PhyloP100

-4.2

Mutation Taster

=94/6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-105361304-G-A

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