chr11-35189914-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000610.4(CD44):​c.516C>A​(p.Asn172Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

CD44
NM_000610.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.366
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]

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ACMG classification

Classification made for transcript

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=0.09168896).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CD44NM_000610.4 linkuse as main transcriptc.516C>A p.Asn172Lys missense_variant 5/18 ENST00000428726.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CD44ENST00000428726.8 linkuse as main transcriptc.516C>A p.Asn172Lys missense_variant 5/181 NM_000610.4 A2P16070-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
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 GeneticsFeb 05, 2024The c.516C>A (p.N172K) alteration is located in exon 5 (coding exon 5) of the CD44 gene. This alteration results from a C to A substitution at nucleotide position 516, causing the asparagine (N) at amino acid position 172 to be replaced by a lysine (K). 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
0.24
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
12
DANN
Benign
0.95
DEOGEN2
Uncertain
0.77
.;D;.;.;.;.;.;T;.;.;T;.
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.075
N
LIST_S2
Uncertain
0.91
D;D;D;D;D;D;D;D;D;D;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.092
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L;L;L;L;.;L;L;.;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-4.2
D;D;D;D;.;D;D;D;D;D;D;D
REVEL
Benign
0.054
Sift
Benign
0.10
T;D;D;D;.;T;T;T;D;D;D;D
Sift4G
Benign
0.28
T;T;T;T;.;T;T;T;T;T;T;D
Polyphen
0.0090
B;B;B;B;.;B;.;.;.;.;.;.
Vest4
0.21
MutPred
0.33
Gain of ubiquitination at N172 (P = 0.0018);Gain of ubiquitination at N172 (P = 0.0018);Gain of ubiquitination at N172 (P = 0.0018);Gain of ubiquitination at N172 (P = 0.0018);Gain of ubiquitination at N172 (P = 0.0018);Gain of ubiquitination at N172 (P = 0.0018);Gain of ubiquitination at N172 (P = 0.0018);.;.;.;.;.;
MVP
0.15
MPC
0.063
ClinPred
0.11
T
GERP RS
2.6
Varity_R
0.15
gMVP
0.32

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

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

Other links and lift over

dbSNP: rs901729150; hg19: chr11-35211461; API