rs199544459

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003737.4(DCHS1):c.4555C>T(p.Pro1519Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,549,598 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 11 hom. )

Consequence

DCHS1
NM_003737.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:2

Conservation

PhyloP100: 3.50

Variant links:

Genes affected

DCHS1 (HGNC:13681): (dachsous cadherin-related 1) This gene is a member of the cadherin superfamily whose members encode calcium-dependent cell-cell adhesion molecules. The encoded protein has a signal peptide, 27 cadherin repeat domains and a unique cytoplasmic region. This particular cadherin family member is expressed in fibroblasts but not in melanocytes or keratinocytes. The cell-cell adhesion of fibroblasts is thought to be necessary for wound healing. [provided by RefSeq, Jul 2008]

DCHS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008468181).

BP6

Variant 11-6630239-G-A is Benign according to our data. Variant chr11-6630239-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 376906.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=3}. Variant chr11-6630239-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00146 (222/152060) while in subpopulation NFE AF= 0.00259 (176/67940). AF 95% confidence interval is 0.00228. There are 0 homozygotes in gnomad4. There are 99 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCHS1	NM_003737.4 link	c.4555C>T	p.Pro1519Ser	missense_variant	Exon 10 of 21	ENST00000299441.5	NP_003728.1	Q96JQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCHS1	ENST00000299441.5 link	c.4555C>T	p.Pro1519Ser	missense_variant	Exon 10 of 21	1	NM_003737.4	ENSP00000299441.3		Q96JQ0

Frequencies

GnomAD3 genomes

AF:

0.00146

AC:

222

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00259

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00133

AC:

197

AN:

147812

Hom.:

AF XY:

0.00138

AC XY:

112

AN XY:

81250

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.000235

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000205

Gnomad NFE exome

AF:

0.00309

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00257

AC:

3585

AN:

1397538

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

1672

AN XY:

690502

show subpopulations

Gnomad4 AFR exome

AF:

0.000284

Gnomad4 AMR exome

AF:

0.000244

Gnomad4 ASJ exome

AF:

0.0000794

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000250

Gnomad4 FIN exome

AF:

0.000530

Gnomad4 NFE exome

AF:

0.00322

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00146

AC:

222

AN:

152060

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.00259

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00274

Hom.:

Bravo

AF:

0.00151

ESP6500AA

AF:

0.000565

AC:

ESP6500EA

AF:

0.000996

AC:

ExAC

AF:

0.000872

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:3Benign:2

Jan 20, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter