rs2740379

Variant names:

• chr11-617967-C-G
• rs2740379
• NM_021924.5:c.2105G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-617967-C-G
• chr11-617967-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021924.5(CDHR5):​c.2105G>C​(p.Cys702Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,611,674 control chromosomes in the GnomAD database, including 800,014 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.98 (73235 hom., cov: 29)
  • Exomes 𝑓: 1.0 (726779 hom.)
• Consequence: CDHR5 NM_021924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.6029924E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR5	NM_021924.5	c.2105G>C	p.Cys702Ser	missense_variant	Exon 14 of 15	ENST00000397542.7	NP_068743.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR5	ENST00000397542.7	c.2105G>C	p.Cys702Ser	missense_variant	Exon 14 of 15	1	NM_021924.5	ENSP00000380676.2

Frequencies

GnomAD3 genomes AF: 0.981 AC: 149070 AN: 151928 Hom.: 73186 Cov.: 29

Gnomad AFR AF: 0.934

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.988

GnomAD3 exomes AF: 0.995 AC: 242544 AN: 243750 Hom.: 120703 AF XY: 0.996 AC XY: 132022 AN XY: 132496

Gnomad AFR exome AF: 0.932

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.998 AC: 1456489 AN: 1459628 Hom.: 726779 Cov.: 55 AF XY: 0.998 AC XY: 724606 AN XY: 725970

Gnomad4 AFR exome AF: 0.925

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.996

GnomAD4 genome AF: 0.981 AC: 149177 AN: 152046 Hom.: 73235 Cov.: 29 AF XY: 0.982 AC XY: 72985 AN XY: 74328

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.994

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.988

Alfa AF: 0.939 Hom.: 20876

Bravo AF: 0.978

TwinsUK AF: 1.00 AC: 3708

ALSPAC AF: 1.00 AC: 3854

ESP6500AA AF: 0.936 AC: 4120

ESP6500EA AF: 1.00 AC: 8594

ExAC AF: 0.994 AC: 120154

Asia WGS AF: 0.994 AC: 3456 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.5
DANN	Benign	0.70
DEOGEN2	Benign	0.0024	T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00021	N
LIST_S2	Benign	0.075	T;.;T
MetaRNN	Benign	6.6e-7	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	3.3	N;N;N
REVEL	Benign	0.025
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.13
MutPred		0.36		Gain of disorder (P = 0.0063);Gain of disorder (P = 0.0063);.;
MPC		0.049
ClinPred		0.0036	T
GERP RS		1.1
Varity_R		0.082
gMVP		0.11

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: rs2740379; hg19: chr11-617967; COSMIC: COSV57645211; COSMIC: COSV57645211;