chr13-38690553-T-G

Variant names:

• chr13-38690553-T-G
• NM_207361.6:c.3209T>G

Variant summary

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

The NM_207361.6(FREM2):​c.3209T>G​(p.Phe1070Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1070S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FREM2 NM_207361.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679

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]

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=0.19840154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FREM2	NM_207361.6	c.3209T>G	p.Phe1070Cys	missense_variant	Exon 1 of 24	ENST00000280481.9	NP_997244.4
FREM2	XM_017020554.2	c.3209T>G	p.Phe1070Cys	missense_variant	Exon 1 of 3		XP_016876043.1
FREM2	XR_941571.3	n.3477T>G		non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FREM2	ENST00000280481.9	c.3209T>G	p.Phe1070Cys	missense_variant	Exon 1 of 24	1	NM_207361.6	ENSP00000280481.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461846 Hom.: 0 Cov.: 40 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.87
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.91	T
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.17
Sift	Benign	0.17	T
Sift4G	Benign	0.19	T
Vest4		0.26
MutPred		0.40		Loss of sheet (P = 0.1907);
MVP		0.49
MPC		0.18
ClinPred		0.19	T
GERP RS		6.1
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-39264690;