17-44899705-T-G

Position:

• chr17-44899705-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000577339.5(CCDC103):​c.-10+175T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,168 control chromosomes in the GnomAD database, including 5,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5293 hom., cov: 31)
  • Exomes 𝑓: 0.38 (8 hom.)
• Consequence: CCDC103 ENST00000577339.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.431

Genes affected

CCDC103 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-44899705-T-G is Benign according to our data. Variant chr17-44899705-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 369146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC103	NM_213607.3			upstream_gene_variant		ENST00000417826.3	NP_998772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC103	ENST00000417826.3			upstream_gene_variant		1	NM_213607.3	ENSP00000391692	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38702 AN: 151948 Hom.: 5278 Cov.: 31

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.382 AC: 39 AN: 102 Hom.: 8 Cov.: 0 AF XY: 0.414 AC XY: 29 AN XY: 70

Gnomad4 AFR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.255 AC: 38754 AN: 152066 Hom.: 5293 Cov.: 31 AF XY: 0.252 AC XY: 18709 AN XY: 74346

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.202

Alfa AF: 0.236 Hom.: 692

Bravo AF: 0.265

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2277617; hg19: chr17-42977073;