Variant rs2071616 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 ENST00000358487.10(FGFR2):c.749-112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,131,798 control chromosomes in the GnomAD database, including 51,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5686 hom., cov: 33)

Exomes 𝑓: 0.30 ( 45786 hom. )

Consequence

FGFR2
ENST00000358487.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.324

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=-0.63).

BP6

Variant 10-121520281-C-T is Benign according to our data. Variant chr10-121520281-C-T is described in ClinVar as [Benign]. Clinvar id is 1262737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-121520281-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR2	NM_000141.5 linkuse as main transcript	c.749-112G>A		intron_variant		ENST00000358487.10	NP_000132.3
FGFR2	NM_022970.4 linkuse as main transcript	c.749-112G>A		intron_variant		ENST00000457416.7	NP_075259.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR2	ENST00000358487.10 linkuse as main transcript	c.749-112G>A		intron_variant		1	NM_000141.5	ENSP00000351276	A2	P21802-1
FGFR2	ENST00000457416.7 linkuse as main transcript	c.749-112G>A		intron_variant		1	NM_022970.4	ENSP00000410294	P4	P21802-3

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38057

AN:

152040

Hom.:

5686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.0916

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.299

AC:

292708

AN:

979640

Hom.:

45786

AF XY:

0.298

AC XY:

144540

AN XY:

485376

show subpopulations

Gnomad4 AFR exome

AF:

0.0990

Gnomad4 AMR exome

AF:

0.241

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.0978

Gnomad4 SAS exome

AF:

0.262

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.317

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.250

AC:

38064

AN:

152158

Hom.:

5686

Cov.:

AF XY:

0.254

AC XY:

18899

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.248

Gnomad4 ASJ

AF:

0.261

Gnomad4 EAS

AF:

0.0916

Gnomad4 SAS

AF:

0.258

Gnomad4 FIN

AF:

0.414

Gnomad4 NFE

AF:

0.324

Gnomad4 OTH

AF:

0.243

Alfa

AF:

0.273

Hom.:

1266

Bravo

AF:

0.228

Asia WGS

AF:

0.193

AC:

672

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	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.51

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