13-38856177-C-T

Position:

chr13-38856177-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207361.6(FREM2):c.6977C>T(p.Thr2326Ile) variant causes a missense change. The variant allele was found at a frequency of 0.717 in 1,610,012 control chromosomes in the GnomAD database, including 416,843 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41391 hom., cov: 31)

Exomes 𝑓: 0.71 ( 375452 hom. )

Consequence

FREM2
NM_207361.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 6.12

Variant links:

Genes affected

FREM2 (HGNC:25396): (FRAS1 related extracellular matrix 2) This gene encodes an integral membrane protein containing numerous CSPG (chondroitin sulfate proteoglycan element) repeats and Calx-beta domains. The encoded protein localizes to the basement membrane, forming a ternary complex that plays a role in epidermal-dermal interactions. This protein is important for the integrity of skin and renal epithelia. Mutations in this gene are associated with Fraser syndrome. [provided by RefSeq, Apr 2014]

FREM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.068395E-7).

BP6

Variant 13-38856177-C-T is Benign according to our data. Variant chr13-38856177-C-T is described in ClinVar as [Benign]. Clinvar id is 263300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-38856177-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FREM2	NM_207361.6 linkuse as main transcript	c.6977C>T	p.Thr2326Ile	missense_variant	12/24	ENST00000280481.9	NP_997244.4	Q5SZK8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FREM2	ENST00000280481.9 linkuse as main transcript	c.6977C>T	p.Thr2326Ile	missense_variant	12/24	1	NM_207361.6	ENSP00000280481.7		Q5SZK8-1

Frequencies

GnomAD3 genomes

AF:

0.735

AC:

111649

AN:

151862

Hom.:

41344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.753

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.775

Gnomad ASJ

AF:

0.725

Gnomad EAS

AF:

0.968

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.742

Gnomad MID

AF:

0.705

Gnomad NFE

AF:

0.699

Gnomad OTH

AF:

0.730

GnomAD3 exomes

AF:

0.749

AC:

188242

AN:

251354

Hom.:

71285

AF XY:

0.741

AC XY:

100727

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.750

Gnomad AMR exome

AF:

0.836

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.971

Gnomad SAS exome

AF:

0.718

Gnomad FIN exome

AF:

0.746

Gnomad NFE exome

AF:

0.698

Gnomad OTH exome

AF:

0.728

GnomAD4 exome

AF:

0.715

AC:

1042168

AN:

1458032

Hom.:

375452

Cov.:

AF XY:

0.715

AC XY:

518764

AN XY:

725570

show subpopulations

Gnomad4 AFR exome

AF:

0.752

Gnomad4 AMR exome

AF:

0.830

Gnomad4 ASJ exome

AF:

0.726

Gnomad4 EAS exome

AF:

0.972

Gnomad4 SAS exome

AF:

0.715

Gnomad4 FIN exome

AF:

0.748

Gnomad4 NFE exome

AF:

0.698

Gnomad4 OTH exome

AF:

0.723

GnomAD4 genome

AF:

0.735

AC:

111754

AN:

151980

Hom.:

41391

Cov.:

AF XY:

0.737

AC XY:

54733

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.753

Gnomad4 AMR

AF:

0.775

Gnomad4 ASJ

AF:

0.725

Gnomad4 EAS

AF:

0.967

Gnomad4 SAS

AF:

0.723

Gnomad4 FIN

AF:

0.742

Gnomad4 NFE

AF:

0.699

Gnomad4 OTH

AF:

0.729

Alfa

AF:

0.714

Hom.:

82527

Bravo

AF:

0.742

TwinsUK

AF:

0.693

AC:

2569

ALSPAC

AF:

0.714

AC:

2751

ESP6500AA

AF:

0.764

AC:

3365

ESP6500EA

AF:

0.700

AC:

6024

ExAC

AF:

0.740

AC:

89796

Asia WGS

AF:

0.817

AC:

2844

AN:

3478

EpiCase

AF:

0.695

EpiControl

AF:

0.695

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Fraser syndrome 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 10, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

Fraser syndrome 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Isolated cryptophthalmia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.017

MetaRNN

Benign

7.1e-7

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.43

PROVEAN

Benign

2.3

REVEL

Benign

0.13

Sift

Benign

0.26

Sift4G

Benign

0.080

Vest4

0.044

MPC

0.13

ClinPred

0.016

GERP RS

5.7

gMVP

0.083

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