7-105974883-G-A

Position:

• chr7-105974883-G-A

Variant summary

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

The NM_152750.5(CDHR3):​c.86G>A​(p.Gly29Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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: 0.0000021 (0 hom.)
• Consequence: CDHR3 NM_152750.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98

Genes affected

CDHR3 (HGNC:26308): (cadherin related family member 3) Predicted to enable cadherin binding activity and calcium ion binding activity. Predicted to be involved in calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; cell morphogenesis; and cell-cell junction organization. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CDHR3 (HGNC:):

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=0.12342256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR3	NM_152750.5	c.86G>A	p.Gly29Asp	missense_variant	2/19	ENST00000317716.14	NP_689963.2
CDHR3	NM_001301161.2	c.-15-6085G>A		intron_variant			NP_001288090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR3	ENST00000317716.14	c.86G>A	p.Gly29Asp	missense_variant	2/19	1	NM_152750.5	ENSP00000325954.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461434 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727010

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.86G>A (p.G29D) alteration is located in exon 2 (coding exon 2) of the CDHR3 gene. This alteration results from a G to A substitution at nucleotide position 86, causing the glycine (G) at amino acid position 29 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.050
Sift	Benign	0.084	T
Sift4G	Benign	0.099	T
Polyphen		0.50	P
Vest4		0.41
MutPred		0.48		Loss of sheet (P = 0.1158);
MVP		0.15
MPC		0.048
ClinPred		0.37	T
GERP RS		3.6
Varity_R		0.24
gMVP		0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs1274627697; hg19: chr7-105615329;