rs2421826

Variant names:

• chr11-35209058-G-A
• rs2421826
• NM_000610.4:c.1516+852G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-35209058-G-A
• chr11-35209058-G-C
• chr11-35209058-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000610.4(CD44):​c.1516+852G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,074 control chromosomes in the GnomAD database, including 33,069 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 0.66 (33069 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 10 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	NM_000610.4	MANE Select	c.1516+852G>A		intron	N/A	NP_000601.3
	CD44	NM_001440324.1		c.1519+852G>A		intron	N/A	NP_001427253.1
	CD44	NM_001440325.1		c.1513+852G>A		intron	N/A	NP_001427254.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.1516+852G>A		intron	N/A	ENSP00000398632.2	P16070-1
	CD44	ENST00000415148.6	TSL:1	c.1387+852G>A		intron	N/A	ENSP00000389830.2	P16070-4
	CD44	ENST00000433892.6	TSL:1	c.769+852G>A		intron	N/A	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99649 AN: 151954 Hom.: 33036 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.644

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.656 AC: 99739 AN: 152074 Hom.: 33069 Cov.: 32 AF XY: 0.663 AC XY: 49305 AN XY: 74326

African (AFR) AF: 0.676 AC: 28040 AN: 41458

American (AMR) AF: 0.726 AC: 11097 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2280 AN: 3472

East Asian (EAS) AF: 0.863 AC: 4471 AN: 5182

South Asian (SAS) AF: 0.750 AC: 3616 AN: 4824

European-Finnish (FIN) AF: 0.628 AC: 6643 AN: 10570

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41471 AN: 67972

Other (OTH) AF: 0.647 AC: 1366 AN: 2112

Alfa AF: 0.630 Hom.: 100627

Bravo AF: 0.663

Asia WGS AF: 0.814 AC: 2830 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.41
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2421826; hg19: chr11-35230605;