rs775311797

Variant names:

• chr11-617482-C-A
• rs775311797
• NM_021924.5:c.2407G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-617482-C-A
• chr11-617482-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021924.5(CDHR5):​c.2407G>T​(p.Val803Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V803M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CDHR5 NM_021924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 2 publications found

Genes affected

CDHR5 (HGNC:7521): (cadherin related family member 5) This gene is a novel mucin-like gene that is a member of the cadherin superfamily. While encoding nonpolymorphic tandem repeats rich in proline, serine and threonine similar to mucin proteins, the gene also contains sequence encoding calcium-binding motifs found in all cadherins. The role of the hybrid extracellular region and the specific function of this protein have not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2010]

ACMG classification

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=0.06848323).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021924.5. 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
	CDHR5	NM_021924.5	MANE Select	c.2407G>T	p.Val803Leu	missense	Exon 15 of 15	NP_068743.3	Q9HBB8-1
	CDHR5	NM_001171968.3		c.2389G>T	p.Val797Leu	missense	Exon 15 of 15	NP_001165439.2	Q9HBB8-4
	CDHR5	NM_031264.5		c.1825G>T	p.Val609Leu	missense	Exon 14 of 14	NP_112554.3	Q9HBB8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR5	ENST00000397542.7	TSL:1 MANE Select	c.2407G>T	p.Val803Leu	missense	Exon 15 of 15	ENSP00000380676.2	Q9HBB8-1
	CDHR5	ENST00000349570.11	TSL:1	c.1825G>T	p.Val609Leu	missense	Exon 14 of 14	ENSP00000345726.7	Q9HBB8-2
	CDHR5	ENST00000872876.1		c.2491G>T	p.Val831Leu	missense	Exon 16 of 16	ENSP00000542935.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00768

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 AF: 0.00000137 AC: 2 AN: 1460402 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726540

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111832

Other (OTH) AF: 0.0000166 AC: 1 AN: 60362

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.084
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.053	T
Polyphen		0.95	P
Vest4		0.20
MutPred		0.23		Loss of sheet (P = 0.0315)
MVP		0.54
MPC		0.11
ClinPred		0.57	D
GERP RS		3.0
Varity_R		0.21
gMVP		0.74
Mutation Taster		=69/31	polymorphism

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: rs775311797; hg19: chr11-617482;