chr13-38689594-C-T

Position:

chr13-38689594-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_207361.6(FREM2):c.2250C>T(p.Asp750=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,612,632 control chromosomes in the GnomAD database, including 10,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 644 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9518 hom. )

Consequence

FREM2
NM_207361.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.177

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 13-38689594-C-T is Benign according to our data. Variant chr13-38689594-C-T is described in ClinVar as [Benign]. Clinvar id is 193537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-38689594-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.177 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FREM2	NM_207361.6 linkuse as main transcript	c.2250C>T	p.Asp750=	synonymous_variant	1/24	ENST00000280481.9	NP_997244.4
FREM2	XM_017020554.2 linkuse as main transcript	c.2250C>T	p.Asp750=	synonymous_variant	1/3		XP_016876043.1
FREM2	XR_941571.3 linkuse as main transcript	n.2518C>T		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FREM2	ENST00000280481.9 linkuse as main transcript	c.2250C>T	p.Asp750=	synonymous_variant	1/24	1	NM_207361.6	ENSP00000280481	P1	Q5SZK8-1

Frequencies

GnomAD3 genomes

AF:

0.0823

AC:

12512

AN:

152016

Hom.:

643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0817

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.0946

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.0937

GnomAD3 exomes

AF:

0.105

AC:

26361

AN:

250408

Hom.:

1611

AF XY:

0.112

AC XY:

15088

AN XY:

135264

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.0732

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.0923

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.109

AC:

159806

AN:

1460498

Hom.:

9518

Cov.:

AF XY:

0.112

AC XY:

81215

AN XY:

726382

show subpopulations

Gnomad4 AFR exome

AF:

0.0170

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.0768

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.0920

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.0822

AC:

12512

AN:

152134

Hom.:

644

Cov.:

AF XY:

0.0836

AC XY:

6213

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0194

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.0817

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.0946

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.0941

Alfa

AF:

0.0740

Hom.:

223

Bravo

AF:

0.0787

Asia WGS

AF:

0.143

AC:

499

AN:

3478

EpiCase

AF:

0.107

EpiControl

AF:

0.108

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 21, 2014	- -

not provided

Benign:2

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

Fraser syndrome 1

Benign:2

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

Fraser syndrome 2

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.4

DANN

Benign

0.66

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