Genetic Variant CD44:p.Ser612Asn (chr11-35214876-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000610.4(CD44):c.1835G>A(p.Ser612Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CD44
NM_000610.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.569

Publications

0 publications found

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]

CD44 links:

CD44-AS1 (HGNC:40133): (CD44 antisense RNA 1)

CD44-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07864773).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000610.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD44	NM_000610.4	MANE Select	c.1835G>A	p.Ser612Asn	missense	Exon 15 of 18	NP_000601.3
CD44	NM_001440324.1		c.1838G>A	p.Ser613Asn	missense	Exon 15 of 18	NP_001427253.1
CD44	NM_001440325.1		c.1832G>A	p.Ser611Asn	missense	Exon 15 of 18	NP_001427254.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD44	ENST00000428726.8	TSL:1 MANE Select	c.1835G>A	p.Ser612Asn	missense	Exon 15 of 18	ENSP00000398632.2	P16070-1
CD44	ENST00000415148.6	TSL:1	c.1706G>A	p.Ser569Asn	missense	Exon 14 of 17	ENSP00000389830.2	P16070-4
CD44	ENST00000433892.6	TSL:1	c.1088G>A	p.Ser363Asn	missense	Exon 9 of 12	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1406396

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698666

African (AFR)

AF:

0.00

AC:

AN:

31198

American (AMR)

AF:

0.00

AC:

AN:

36778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24666

East Asian (EAS)

AF:

0.00

AC:

AN:

36088

South Asian (SAS)

AF:

0.00

AC:

AN:

77370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084436

Other (OTH)

AF:

0.00

AC:

AN:

57966

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.8

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.41

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.69

M_CAP

Benign

0.0062

MetaRNN

Benign

0.079

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

PhyloP100

0.57

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

REVEL

Benign

0.11

Sift

Benign

0.13

Sift4G

Benign

0.089

Polyphen

0.019

Vest4

0.12

MutPred

0.17

Loss of glycosylation at S612 (P = 0.0012)

MVP

0.40

MPC

0.042

ClinPred

0.055

GERP RS

0.36

Varity_R

0.091

gMVP

0.11

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over