rs922755312

Variant names:

• chr11-617685-T-A
• rs922755312
• NM_021924.5:c.2204A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021924.5(CDHR5):​c.2204A>T​(p.Asp735Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,475,604 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D735N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CDHR5 NM_021924.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.29
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.061115265).

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.2204A>T	p.Asp735Val	missense	Exon 15 of 15	NP_068743.3	Q9HBB8-1
	CDHR5	NM_001171968.3		c.2186A>T	p.Asp729Val	missense	Exon 15 of 15	NP_001165439.2	Q9HBB8-4
	CDHR5	NM_031264.5		c.1622A>T	p.Asp541Val	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.2204A>T	p.Asp735Val	missense	Exon 15 of 15	ENSP00000380676.2	Q9HBB8-1
	CDHR5	ENST00000349570.11	TSL:1	c.1622A>T	p.Asp541Val	missense	Exon 14 of 14	ENSP00000345726.7	Q9HBB8-2
	CDHR5	ENST00000872876.1		c.2288A>T	p.Asp763Val	missense	Exon 16 of 16	ENSP00000542935.1

Frequencies

GnomAD3 genomes AF: 0.0000660 AC: 10 AN: 151470 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000243

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.55e-7 AC: 1 AN: 1324022 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 648028

African (AFR) AF: 0.00 AC: 0 AN: 29260

American (AMR) AF: 0.00 AC: 0 AN: 24278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20058

East Asian (EAS) AF: 0.00 AC: 0 AN: 35576

South Asian (SAS) AF: 0.00 AC: 0 AN: 67600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5126

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1052280

Other (OTH) AF: 0.0000182 AC: 1 AN: 55072

GnomAD4 genome AF: 0.0000660 AC: 10 AN: 151582 Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4 AN XY: 74080

African (AFR) AF: 0.000242 AC: 10 AN: 41264

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67866

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.28
DANN	Benign	0.56
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.3
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.044
Sift	Uncertain	0.027	D
Sift4G	Benign	0.16	T
Polyphen		0.21	B
Vest4		0.097
MutPred		0.095		Loss of solvent accessibility (P = 0.0907)
MVP		0.081
MPC		0.073
ClinPred		0.19	T
GERP RS		-0.63
Varity_R		0.091
gMVP		0.22
Mutation Taster		=88/12	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: rs922755312; hg19: chr11-617685;