NM_021924.5:c.2294C>A

Variant names:

• chr11-617595-G-T
• rs779084236
• NM_021924.5:c.2294C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021924.5(CDHR5):​c.2294C>A​(p.Ala765Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,455,628 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CDHR5 NM_021924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1113936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR5	NM_021924.5	c.2294C>A	p.Ala765Asp	missense_variant	Exon 15 of 15	ENST00000397542.7	NP_068743.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR5	ENST00000397542.7	c.2294C>A	p.Ala765Asp	missense_variant	Exon 15 of 15	1	NM_021924.5	ENSP00000380676.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000434 AC: 1 AN: 230398 Hom.: 0 AF XY: 0.00000785 AC XY: 1 AN XY: 127342

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1455628 Hom.: 0 Cov.: 36 AF XY: 0.00000553 AC XY: 4 AN XY: 723940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000844 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0094	T;T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.40	T;.;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.4	N;N;D
REVEL	Benign	0.053
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.99	D;D;P
Vest4		0.18
MutPred		0.26		Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);.;
MVP		0.31
MPC		0.18
ClinPred		0.78	D
GERP RS		0.47
Varity_R		0.40
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs779084236; hg19: chr11-617595;