chr16-84165762-GTTTC-G

Variant names:

• chr16-84165762-GTTTC-G
• rs141073777
• NM_178452.6:c.864-17_864-14delCTTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_178452.6(DNAAF1):​c.864-17_864-14delCTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00709 in 1,611,678 control chromosomes in the GnomAD database, including 664 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (321 hom., cov: 31)
  • Exomes 𝑓: 0.0039 (343 hom.)
• Consequence: DNAAF1 NM_178452.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.724
• Publications: 1 publications found

Genes affected

DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DNAAF1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 16-84165762-GTTTC-G is Benign according to our data. Variant chr16-84165762-GTTTC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 179948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6	c.864-17_864-14delCTTT		intron_variant	Intron 6 of 11	ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10	c.864-20_864-17delTTTC		intron_variant	Intron 6 of 11	1	NM_178452.6	ENSP00000367815.5

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5645 AN: 151928 Hom.: 319 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0206

GnomAD2 exomes AF: 0.00982 AC: 2465 AN: 251072 AF XY: 0.00714

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.00679

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000344

Gnomad OTH exome AF: 0.00474

GnomAD4 exome AF: 0.00395 AC: 5759 AN: 1459632 Hom.: 343 AF XY: 0.00341 AC XY: 2474 AN XY: 726288

African (AFR) AF: 0.136 AC: 4532 AN: 33420

American (AMR) AF: 0.00787 AC: 352 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.000360 AC: 31 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00777 AC: 42 AN: 5406

European-Non Finnish (NFE) AF: 0.000213 AC: 237 AN: 1110462

Other (OTH) AF: 0.00936 AC: 564 AN: 60274

GnomAD4 genome AF: 0.0372 AC: 5660 AN: 152046 Hom.: 321 Cov.: 31 AF XY: 0.0368 AC XY: 2733 AN XY: 74340

African (AFR) AF: 0.130 AC: 5382 AN: 41430

American (AMR) AF: 0.0130 AC: 198 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 67986

Other (OTH) AF: 0.0203 AC: 43 AN: 2114

Alfa AF: 0.0169 Hom.: 24

Bravo AF: 0.0434

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

864-17_864-14delCTTT in intron 6 of DNAAF1: This variant is not expected to have clinical significance because at is a deletion of 4 bases but does not diverge from the splice consensus sequence and is therefore unlikely to impact splicing. This variant has been reported in dbSNP without frequency information (rs141073 777). -

Primary ciliary dyskinesia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs141073777; hg19: chr16-84199368;