Variant chr8-38404715-T-C 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_001286819.2(LETM2):c.1218+209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 513,832 control chromosomes in the GnomAD database, including 11,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3299 hom., cov: 33)

Exomes 𝑓: 0.21 ( 8188 hom. )

Consequence

LETM2
NM_001286819.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.69

Variant links:

Genes affected

LETM2 (HGNC:14648): (leucine zipper and EF-hand containing transmembrane protein 2) Predicted to enable ribosome binding activity. Predicted to be involved in cellular metal ion homeostasis. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LETM2 links:

FGFR1 (HGNC:3688): (fibroblast growth factor receptor 1) The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) 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 binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

FGFR1 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=-0.99).

BP6

Variant 8-38404715-T-C is Benign according to our data. Variant chr8-38404715-T-C is described in ClinVar as [Benign]. Clinvar id is 1261324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LETM2	NM_001286819.2 linkuse as main transcript	c.1218+209T>C		intron_variant		ENST00000379957.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LETM2	ENST00000379957.9 linkuse as main transcript	c.1218+209T>C		intron_variant		5	NM_001286819.2	P4	Q2VYF4-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30435

AN:

152066

Hom.:

3293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.205

GnomAD4 exome

AF:

0.206

AC:

74652

AN:

361648

Hom.:

8188

Cov.:

AF XY:

0.200

AC XY:

38652

AN XY:

193024

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.247

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.351

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.200

AC:

30466

AN:

152184

Hom.:

3299

Cov.:

AF XY:

0.197

AC XY:

14649

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.243

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.339

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.218

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.194

Hom.:

376

Bravo

AF:

0.210

Asia WGS

AF:

0.212

AC:

735

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	Oct 29, 2020	This variant is associated with the following publications: (PMID: 32747698) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.098

DANN

Benign

0.26

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