9-71685844-G-C

Variant summary

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

The NM_013390.3(CEMIP2):​c.3854C>G​(p.Ser1285Cys) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CEMIP2
NM_013390.3 missense, splice_region

Scores

5
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81
Variant links:
Genes affected
CEMIP2 (HGNC:11869): (cell migration inducing hyaluronidase 2) This gene encodes a type II transmembrane protein that belongs to the interferon-induced transmembrane (IFITM) protein superfamily. The encoded protein functions as a cell surface hyaluronidase that cleaves extracellular high molecular weight hyaluronan into intermediate size fragments before internalization and degradation in the lysosome. It also has an interferon-mediated antiviral function in humans through activation of the JAK STAT signaling pathway. The activation of this gene by transcription factor SOX4 in breast cancer cells has been shown to mediate the pathological effects of SOX4 on cancer progression. Naturally occurring mutations in this gene are associated with autosomal recessive non-syndromic hearing loss. [provided by RefSeq, Mar 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CEMIP2NM_013390.3 linkc.3854C>G p.Ser1285Cys missense_variant, splice_region_variant 23/24 ENST00000377044.9 NP_037522.1 Q9UHN6-1A0A024R229

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CEMIP2ENST00000377044.9 linkc.3854C>G p.Ser1285Cys missense_variant, splice_region_variant 23/241 NM_013390.3 ENSP00000366243.4 Q9UHN6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 11, 2024The c.3854C>G (p.S1285C) alteration is located in exon 23 (coding exon 22) of the TMEM2 gene. This alteration results from a C to G substitution at nucleotide position 3854, causing the serine (S) at amino acid position 1285 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.24
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;.;T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.082
D
MetaRNN
Uncertain
0.61
D;D;D
MetaSVM
Uncertain
0.36
D
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.9
D;D;D
REVEL
Uncertain
0.53
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.58
MutPred
0.62
Loss of phosphorylation at S1285 (P = 0.0484);.;.;
MVP
0.81
MPC
0.67
ClinPred
0.99
D
GERP RS
5.7
Varity_R
0.55
gMVP
0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1223823387; hg19: chr9-74300760; API