chr11-35176617-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000610.4(CD44):​c.110A>C​(p.Glu37Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

CD44
NM_000610.4 missense

Scores

7
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38
Variant links:
Genes affected
CD44 (HGNC:1681): (CD44 molecule (IN blood group)) The protein encoded by this gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.763

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CD44NM_000610.4 linkuse as main transcriptc.110A>C p.Glu37Ala missense_variant 2/18 ENST00000428726.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CD44ENST00000428726.8 linkuse as main transcriptc.110A>C p.Glu37Ala missense_variant 2/181 NM_000610.4 A2P16070-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

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 GeneticsJan 24, 2023The c.110A>C (p.E37A) alteration is located in exon 2 (coding exon 2) of the CD44 gene. This alteration results from a A to C substitution at nucleotide position 110, causing the glutamic acid (E) at amino acid position 37 to be replaced by an alanine (A). 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
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.45
.;T;T;.;T;.;.;.;.;.
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Pathogenic
0.76
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.6
M;M;.;M;.;M;.;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-5.5
D;D;D;D;.;D;.;D;D;D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0030
D;D;D;D;.;D;.;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;.;D;D;D
Polyphen
1.0
D;D;.;D;.;D;.;.;D;.
Vest4
0.69
MutPred
0.61
Loss of ubiquitination at K38 (P = 0.0504);Loss of ubiquitination at K38 (P = 0.0504);Loss of ubiquitination at K38 (P = 0.0504);Loss of ubiquitination at K38 (P = 0.0504);Loss of ubiquitination at K38 (P = 0.0504);Loss of ubiquitination at K38 (P = 0.0504);Loss of ubiquitination at K38 (P = 0.0504);Loss of ubiquitination at K38 (P = 0.0504);Loss of ubiquitination at K38 (P = 0.0504);Loss of ubiquitination at K38 (P = 0.0504);
MVP
0.53
MPC
1.9
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.90
gMVP
0.90

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: chr11-35198164; API