Genetic Variant CD44:c.*2392C>T (chr11-35231725-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000610.4(CD44):c.*2392C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,050 control chromosomes in the GnomAD database, including 11,469 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 11469 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

CD44
NM_000610.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.00

Publications

63 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

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	Effect	Exon Rank	Protein
CD44	NM_000610.4	MANE Select	c.*2392C>T	3_prime_UTR	Exon 18 of 18	NP_000601.3
CD44	NM_001440324.1		c.*2392C>T	3_prime_UTR	Exon 18 of 18	NP_001427253.1
CD44	NM_001440325.1		c.*2392C>T	3_prime_UTR	Exon 18 of 18	NP_001427254.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD44	ENST00000428726.8	TSL:1 MANE Select	c.*2392C>T	3_prime_UTR	Exon 18 of 18	ENSP00000398632.2	P16070-1
CD44	ENST00000263398.11	TSL:1	c.*2392C>T	3_prime_UTR	Exon 9 of 9	ENSP00000263398.6	P16070-12
CD44	ENST00000904013.1		c.*2392C>T	3_prime_UTR	Exon 18 of 18	ENSP00000574072.1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51882

AN:

151932

Hom.:

11449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.633

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.317

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.342

AC:

51952

AN:

152050

Hom.:

11469

Cov.:

AF XY:

0.339

AC XY:

25169

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.633

AC:

26251

AN:

41470

American (AMR)

AF:

0.320

AC:

4888

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

842

AN:

3472

East Asian (EAS)

AF:

0.323

AC:

1671

AN:

5172

South Asian (SAS)

AF:

0.173

AC:

832

AN:

4816

European-Finnish (FIN)

AF:

0.240

AC:

2540

AN:

10566

Middle Eastern (MID)

AF:

0.322

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.207

AC:

14039

AN:

67978

Other (OTH)

AF:

0.313

AC:

662

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1495

2991

4486

5982

7477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.249

Hom.:

19268

Bravo

AF:

0.365

Asia WGS

AF:

0.254

AC:

883

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.084

(source)

DANN

Benign

0.54

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over