7-741475-C-T

Variant names:

• chr7-741475-C-T
• rs375071932
• NM_017802.4:c.1024+10C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_017802.4(DNAAF5):​c.1024+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,492,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: DNAAF5 NM_017802.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08
• Publications: 0 publications found

Genes affected

DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

DNAAF5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 18

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-741475-C-T is Benign according to our data. Variant chr7-741475-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 260918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000329 (50/152108) while in subpopulation NFE AF = 0.000471 (32/67974). AF 95% confidence interval is 0.000342. There are 0 homozygotes in GnomAd4. There are 22 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4	c.1024+10C>T		intron_variant	Intron 4 of 12	ENST00000297440.11	NP_060272.3
DNAAF5	NR_075098.2	n.984+10C>T		intron_variant	Intron 4 of 12
DNAAF5	XM_024446813.2	c.1024+10C>T		intron_variant	Intron 4 of 11		XP_024302581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11	c.1024+10C>T		intron_variant	Intron 4 of 12	1	NM_017802.4	ENSP00000297440.6
DNAAF5	ENST00000440747.5	c.427+10C>T		intron_variant	Intron 4 of 12	2		ENSP00000403165.1
DNAAF5	ENST00000437419.5	c.340+10C>T		intron_variant	Intron 3 of 4	5		ENSP00000410788.1
DNAAF5	ENST00000438961.1	n.493+10C>T		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 151990 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000130 AC: 23 AN: 176454 AF XY: 0.0000858

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000391

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000289

Gnomad OTH exome AF: 0.000212

GnomAD4 exome AF: 0.000205 AC: 275 AN: 1340842 Hom.: 0 Cov.: 21 AF XY: 0.000209 AC XY: 139 AN XY: 665550

African (AFR) AF: 0.0000634 AC: 2 AN: 31530

American (AMR) AF: 0.0000274 AC: 1 AN: 36534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24562

East Asian (EAS) AF: 0.0000531 AC: 2 AN: 37674

South Asian (SAS) AF: 0.0000254 AC: 2 AN: 78634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4518

European-Non Finnish (NFE) AF: 0.000248 AC: 253 AN: 1021256

Other (OTH) AF: 0.000267 AC: 15 AN: 56136

GnomAD4 genome AF: 0.000329 AC: 50 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22 AN XY: 74364

African (AFR) AF: 0.0000482 AC: 2 AN: 41524

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000471 AC: 32 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000126 Hom.: 0

Bravo AF: 0.000359

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.32
DANN	Benign	0.26
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs375071932; hg19: chr7-781112;