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rs2981582

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000141.5(FGFR2):c.109+906T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,896 control chromosomes in the GnomAD database, including 26,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.58 ( 26097 hom., cov: 31)

Consequence

FGFR2
NM_000141.5 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.827
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 10-121592803-A-G is Benign according to our data. Variant chr10-121592803-A-G is described in ClinVar as [Benign]. Clinvar id is 36931.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGFR2NM_000141.5 linkuse as main transcriptc.109+906T>C intron_variant ENST00000358487.10
FGFR2NM_022970.4 linkuse as main transcriptc.109+906T>C intron_variant ENST00000457416.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGFR2ENST00000358487.10 linkuse as main transcriptc.109+906T>C intron_variant 1 NM_000141.5 A2P21802-1
FGFR2ENST00000457416.7 linkuse as main transcriptc.109+906T>C intron_variant 1 NM_022970.4 P4P21802-3

Frequencies

GnomAD3 genomes
AF:
0.584
AC:
88710
AN:
151778
Hom.:
26072
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.521
Gnomad AMI
AF:
0.436
Gnomad AMR
AF:
0.590
Gnomad ASJ
AF:
0.576
Gnomad EAS
AF:
0.689
Gnomad SAS
AF:
0.653
Gnomad FIN
AF:
0.578
Gnomad MID
AF:
0.554
Gnomad NFE
AF:
0.613
Gnomad OTH
AF:
0.585
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.584
AC:
88779
AN:
151896
Hom.:
26097
Cov.:
31
AF XY:
0.583
AC XY:
43295
AN XY:
74216
show subpopulations
Gnomad4 AFR
AF:
0.521
Gnomad4 AMR
AF:
0.590
Gnomad4 ASJ
AF:
0.576
Gnomad4 EAS
AF:
0.689
Gnomad4 SAS
AF:
0.652
Gnomad4 FIN
AF:
0.578
Gnomad4 NFE
AF:
0.613
Gnomad4 OTH
AF:
0.589
Alfa
AF:
0.604
Hom.:
52956
Bravo
AF:
0.581
Asia WGS
AF:
0.665
AC:
2311
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

FGFR2-related craniosynostosis Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
14
Dann
Benign
0.64

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.

Other links and lift over

dbSNP: rs2981582; hg19: chr10-123352317; COSMIC: COSV60638493; API