Variant 9-71690242-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3

The NM_013390.3(CEMIP2):c.3701A>G(p.Asn1234Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CEMIP2
NM_013390.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73

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]

CEMIP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity CEIP2_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEMIP2	NM_013390.3 linkuse as main transcript	c.3701A>G	p.Asn1234Ser	missense_variant	22/24	ENST00000377044.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEMIP2	ENST00000377044.9 linkuse as main transcript	c.3701A>G	p.Asn1234Ser	missense_variant	22/24	1	NM_013390.3	P1	Q9UHN6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461252

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.3701A>G (p.N1234S) alteration is located in exon 22 (coding exon 21) of the TMEM2 gene. This alteration results from a A to G substitution at nucleotide position 3701, causing the asparagine (N) at amino acid position 1234 to be replaced by a serine (S). 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

0.092

BayesDel_addAF

Benign

0.0082

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Uncertain

0.087

MetaRNN

Pathogenic

0.79

D;D;D

MetaSVM

Uncertain

0.27

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.71

MutPred

0.57

Gain of glycosylation at N1234 (P = 0.0141);.;.;

MVP

0.79

MPC

0.33

ClinPred

0.93

GERP RS

5.8

Varity_R

0.26

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over