chr10-121478354-ATTTAT-A

Position:

chr10-121478354-ATTTAT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000141.5(FGFR2):c.*1498_*1502del variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00272 in 152,326 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00099 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FGFR2
NM_000141.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:9

Conservation

PhyloP100: 5.74

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 10-121478354-ATTTAT-A is Benign according to our data. Variant chr10-121478354-ATTTAT-A is described in ClinVar as [Likely_benign]. Clinvar id is 298974.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00272 (415/152326) while in subpopulation AMR AF= 0.0242 (370/15300). AF 95% confidence interval is 0.0222. There are 4 homozygotes in gnomad4. There are 239 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 Mitochondrial gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR2	NM_000141.5 linkuse as main transcript	c.1498_1502del		3_prime_UTR_variant	18/18	ENST00000358487.10	NP_000132.3
FGFR2	NM_022970.4 linkuse as main transcript	c.1498_1502del		3_prime_UTR_variant	18/18	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.1498_1502del		3_prime_UTR_variant	18/18	1	NM_000141.5	ENSP00000351276	A2	P21802-1
FGFR2	ENST00000457416.7 linkuse as main transcript	c.1498_1502del		3_prime_UTR_variant	18/18	1	NM_022970.4	ENSP00000410294	P4	P21802-3

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

414

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0241

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000995

AC:

AN:

79406

Hom.:

AF XY:

0.00104

AC XY:

AN XY:

36584

show subpopulations

Gnomad4 AFR exome

AF:

0.000529

Gnomad4 AMR exome

AF:

0.0283

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00272

AC:

415

AN:

152326

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

239

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.0242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00445

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:9

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Crouzon syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pfeiffer syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Beare-Stevenson cutis gyrata syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Isolated coronal synostosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Levy-Hollister syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Jackson-Weiss syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Craniosynostosis syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Acrocephalosyndactyly type I

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Saethre-Chotzen syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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