10-101608897-T-C

Variant names:

• chr10-101608897-T-C
• rs7006
• NM_015448.3:c.467T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001329742.2(DPCD):​c.500T>C​(p.Leu167Ser) 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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6200 hom., cov: 31)
  • Exomes 𝑓: 0.27 (56982 hom.)
• Consequence: DPCD NM_001329742.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.597
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1233427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329742.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPCD	NM_015448.3	MANE Select	c.467T>C	p.Leu156Ser	missense	Exon 5 of 6	NP_056263.1
	DPCD	NM_001329742.2		c.500T>C	p.Leu167Ser	missense	Exon 5 of 6	NP_001316671.1
	DPCD	NM_001329743.2		c.431T>C	p.Leu144Ser	missense	Exon 5 of 6	NP_001316672.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPCD	ENST00000370151.9	TSL:1 MANE Select	c.467T>C	p.Leu156Ser	missense	Exon 5 of 6	ENSP00000359170.4
	DPCD	ENST00000897438.1		c.563T>C	p.Leu188Ser	missense	Exon 6 of 7	ENSP00000567497.1
	DPCD	ENST00000927874.1		c.518T>C	p.Leu173Ser	missense	Exon 6 of 7	ENSP00000597933.1

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

GnomAD2 exomes AF: 0.249 AC: 62484 AN: 251266 AF XY: 0.248

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 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

African (AFR) AF: 0.306 AC: 10241 AN: 33454

American (AMR) AF: 0.186 AC: 8329 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 8575 AN: 26120

East Asian (EAS) AF: 0.133 AC: 5264 AN: 39674

South Asian (SAS) AF: 0.160 AC: 13775 AN: 86248

European-Finnish (FIN) AF: 0.252 AC: 13407 AN: 53172

Middle Eastern (MID) AF: 0.247 AC: 1422 AN: 5766

European-Non Finnish (NFE) AF: 0.291 AC: 323698 AN: 1111198

Other (OTH) AF: 0.279 AC: 16805 AN: 60326

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

African (AFR) AF: 0.303 AC: 12542 AN: 41412

American (AMR) AF: 0.253 AC: 3853 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3464

East Asian (EAS) AF: 0.160 AC: 825 AN: 5150

South Asian (SAS) AF: 0.152 AC: 730 AN: 4808

European-Finnish (FIN) AF: 0.250 AC: 2644 AN: 10582

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.295 AC: 20018 AN: 67938

Other (OTH) AF: 0.287 AC: 604 AN: 2108

Alfa AF: 0.290 Hom.: 21595

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.93	T
PhyloP100		0.60
PROVEAN	Benign	0.040	N
REVEL	Benign	0.027
Sift	Pathogenic	0.0	D
Vest4		0.063
ClinPred		0.0094	T
GERP RS		-0.55
Varity_R		0.012
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7006; hg19: chr10-103368654; COSMIC: COSV58707926; COSMIC: COSV58707926;