chr5-128350042-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001999.4(FBN2):c.2813-37C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 1,523,168 control chromosomes in the GnomAD database, including 862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 62 hom., cov: 33)

Exomes 𝑓: 0.032 ( 800 hom. )

Consequence

FBN2
NM_001999.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0510

Publications

3 publications found

Variant links:

Genes affected

FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]

FBN2 Gene-Disease associations (from GenCC):

congenital contractural arachnodactyly
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
carpal tunnel syndrome
Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox
familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
macular degeneration, early-onset
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

FBN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-128350042-G-T is Benign according to our data. Variant chr5-128350042-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 258513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0217 (3301/152212) while in subpopulation NFE AF = 0.0367 (2495/68012). AF 95% confidence interval is 0.0355. There are 62 homozygotes in GnomAd4. There are 1488 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 3301 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4 link	c.2813-37C>A		intron_variant	Intron 21 of 64	ENST00000262464.9	NP_001990.2	P35556-1
FBN2	XM_017009228.3 link	c.2660-37C>A		intron_variant	Intron 20 of 63		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9 link	c.2813-37C>A		intron_variant	Intron 21 of 64	1	NM_001999.4	ENSP00000262464.4		P35556-1
FBN2	ENST00000508989.5 link	c.2714-37C>A		intron_variant	Intron 20 of 32	2		ENSP00000425596.1		D6RJI3

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

3305

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00645

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0142

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.00906

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.0234

AC:

5868

AN:

250322

AF XY:

0.0247

show subpopulations

Gnomad AFR exome

AF:

0.00613

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.0376

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0324

AC:

44484

AN:

1370956

Hom.:

800

Cov.:

AF XY:

0.0320

AC XY:

21996

AN XY:

687358

show subpopulations

African (AFR)

AF:

0.00492

AC:

156

AN:

31738

American (AMR)

AF:

0.0117

AC:

523

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.0171

AC:

437

AN:

25502

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39242

South Asian (SAS)

AF:

0.0189

AC:

1594

AN:

84320

European-Finnish (FIN)

AF:

0.0135

AC:

722

AN:

53328

Middle Eastern (MID)

AF:

0.0235

AC:

132

AN:

5622

European-Non Finnish (NFE)

AF:

0.0381

AC:

39178

AN:

1029254

Other (OTH)

AF:

0.0304

AC:

1741

AN:

57324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1963

3926

5888

7851

9814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0217

AC:

3301

AN:

152212

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

1488

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00640

AC:

266

AN:

41538

American (AMR)

AF:

0.0142

AC:

217

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.0172

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00906

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0367

AC:

2495

AN:

68012

Other (OTH)

AF:

0.0218

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

153

306

460

613

766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0214

Hom.:

Bravo

AF:

0.0210

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 26, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.87

CADD

Benign

1.8

(source)

DANN

Benign

0.40

PhyloP100

-0.051

Mutation Taster

=100/0

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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chr5-128350042-G-T

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