10-121594355-C-T

Position:

• chr10-121594355-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000141.5(FGFR2):​c.-150-388G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,028 control chromosomes in the GnomAD database, including 23,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (23149 hom., cov: 32)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.237

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 10-121594355-C-T is Benign according to our data. Variant chr10-121594355-C-T is described in ClinVar as [Benign]. Clinvar id is 1257485.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR2	NM_000141.5	c.-150-388G>A		intron_variant		ENST00000358487.10	NP_000132.3
FGFR2	NM_022970.4	c.-150-388G>A		intron_variant		ENST00000457416.7	NP_075259.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR2	ENST00000358487.10	c.-150-388G>A		intron_variant		1	NM_000141.5	ENSP00000351276	A2
FGFR2	ENST00000457416.7	c.-150-388G>A		intron_variant		1	NM_022970.4	ENSP00000410294	P4

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83022 AN: 151908 Hom.: 23142 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.546 AC: 83049 AN: 152028 Hom.: 23149 Cov.: 32 AF XY: 0.545 AC XY: 40473 AN XY: 74298

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.554

Alfa AF: 0.580 Hom.: 7049

Bravo AF: 0.539

Asia WGS AF: 0.592 AC: 2059 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.56
CADD	Benign	13
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs3135718; hg19: chr10-123353869;