Variant rs2303568 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000141.5(FGFR2):c.454+54T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,521,000 control chromosomes in the GnomAD database, including 5,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2639 hom., cov: 32)

Exomes 𝑓: 0.018 ( 2602 hom. )

Consequence

FGFR2
NM_000141.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.229

Variant links:

Genes affected

FGFR2 (HGNC:3689): (fibroblast growth factor receptor 2) The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform. Mutations in this gene are associated with Crouzon syndrome, Pfeiffer syndrome, Craniosynostosis, Apert syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrata syndrome, Saethre-Chotzen syndrome, and syndromic craniosynostosis. Multiple alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]

FGFR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-121564448-A-G is Benign according to our data. Variant chr10-121564448-A-G is described in ClinVar as [Benign]. Clinvar id is 1221381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFR2	NM_000141.5 linkuse as main transcript	c.454+54T>C		intron_variant		ENST00000358487.10
FGFR2	NM_022970.4 linkuse as main transcript	c.454+54T>C		intron_variant		ENST00000457416.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFR2	ENST00000358487.10 linkuse as main transcript	c.454+54T>C		intron_variant		1	NM_000141.5	A2	P21802-1
FGFR2	ENST00000457416.7 linkuse as main transcript	c.454+54T>C		intron_variant		1	NM_022970.4	P4	P21802-3

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16661

AN:

151838

Hom.:

2621

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0873

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.0734

Gnomad SAS

AF:

0.00752

Gnomad FIN

AF:

0.0302

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.0822

GnomAD4 exome

AF:

0.0175

AC:

24014

AN:

1369042

Hom.:

2602

Cov.:

AF XY:

0.0154

AC XY:

10543

AN XY:

686418

show subpopulations

Gnomad4 AFR exome

AF:

0.358

Gnomad4 AMR exome

AF:

0.106

Gnomad4 ASJ exome

AF:

0.000702

Gnomad4 EAS exome

AF:

0.0729

Gnomad4 SAS exome

AF:

0.00344

Gnomad4 FIN exome

AF:

0.0288

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.0324

GnomAD4 genome

AF:

0.110

AC:

16727

AN:

151958

Hom.:

2639

Cov.:

AF XY:

0.109

AC XY:

8132

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.0880

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.0726

Gnomad4 SAS

AF:

0.00753

Gnomad4 FIN

AF:

0.0302

Gnomad4 NFE

AF:

0.00262

Gnomad4 OTH

AF:

0.0818

Alfa

AF:

0.0464

Hom.:

207

Bravo

AF:

0.126

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

9.7

DANN

Benign

0.63

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