rs7006

chr10-101608897-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015448.3(DPCD):c.467T>C(p.Leu156Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,612,594 control chromosomes in the GnomAD database, including 63,182 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.28 (6200 hom., cov: 31)
  • Exomes 𝑓: 0.27 (56982 hom.)
• Consequence: DPCD NM_015448.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.597

Genes affected

DPCD (HGNC:24542): (deleted in primary ciliary dyskinesia homolog (mouse)) This gene in mouse encodes a protein that may be involved in the generation and maintenance of ciliated cells. In mouse, expression of this gene increases during ciliated cell differentiation, and disruption of this gene has been linked to primary ciliary dyskinesia. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027190149).
• BP6: Variant 10-101608897-T-C is Benign according to our data. Variant chr10-101608897-T-C is described in ClinVar as [Benign]. Clinvar id is 1233427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPCD	NM_015448.3	c.467T>C	p.Leu156Ser	missense_variant	5/6	ENST00000370151.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPCD	ENST00000370151.9	c.467T>C	p.Leu156Ser	missense_variant	5/6	1	NM_015448.3	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42650 AN: 151802 Hom.: 6195 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.287

GnomAD3 exomes AF: 0.249 AC: 62484 AN: 251266 Hom.: 8424 AF XY: 0.248 AC XY: 33617 AN XY: 135816

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.325

Gnomad EAS exome AF: 0.153

Gnomad SAS exome AF: 0.155

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.275 AC: 401516 AN: 1460676 Hom.: 56982 Cov.: 33 AF XY: 0.272 AC XY: 197615 AN XY: 726682

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.281 AC: 42672 AN: 151918 Hom.: 6200 Cov.: 31 AF XY: 0.275 AC XY: 20457 AN XY: 74262

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.287

Alfa AF: 0.290 Hom.: 16297

Bravo AF: 0.282

TwinsUK AF: 0.284 AC: 1052

ALSPAC AF: 0.286 AC: 1101

ESP6500AA AF: 0.307 AC: 1354

ESP6500EA AF: 0.307 AC: 2639

ExAC AF: 0.250 AC: 30337

Asia WGS AF: 0.143 AC: 499 AN: 3478

EpiCase AF: 0.302

EpiControl AF: 0.304

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 23, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0067	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.31	T;.
MetaRNN	Benign	0.0027	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	P;P;P
Vest4		0.063
ClinPred		0.0094	T
GERP RS		-0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7006; hg19: chr10-103368654; COSMIC: COSV58707926; COSMIC: COSV58707926;