13-38687920-G-C

Position:

• chr13-38687920-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207361.6(FREM2):​c.576G>C​(p.Glu192Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E192E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 36)
• Consequence: FREM2 NM_207361.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1127941).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FREM2	NM_207361.6	c.576G>C	p.Glu192Asp	missense_variant	1/24	ENST00000280481.9	NP_997244.4
FREM2	XM_017020554.2	c.576G>C	p.Glu192Asp	missense_variant	1/3		XP_016876043.1
FREM2	XR_941571.3	n.844G>C		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FREM2	ENST00000280481.9	c.576G>C	p.Glu192Asp	missense_variant	1/24	1	NM_207361.6	ENSP00000280481.7

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.95
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.038
Sift	Benign	0.52	T
Sift4G	Benign	0.21	T
Vest4		0.16
MutPred		0.70		Loss of helix (P = 0.079);
MVP		0.29
MPC		0.11
ClinPred		0.082	T
GERP RS		2.2
gMVP		0.53

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

Other links and lift over

dbSNP: rs1868464; hg19: chr13-39262057;