7-754840-G-T

Variant names:

• chr7-754840-G-T
• rs371368276
• NM_017802.4:c.1257+19G>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.1257+19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000959 in 1,552,912 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 0.00051 (0 hom., cov: 35)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: DNAAF5 NM_017802.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.185
• 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=-0.83).
• BP6: Variant 7-754840-G-T is Benign according to our data. Variant chr7-754840-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000506 (77/152320) while in subpopulation AFR AF = 0.0018 (75/41580). AF 95% confidence interval is 0.00147. There are 0 homozygotes in GnomAd4. There are 36 alleles in the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017802.4. 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
	DNAAF5	NM_017802.4	MANE Select	c.1257+19G>T		intron	N/A	NP_060272.3
	DNAAF5	NR_075098.2		n.1217+19G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.1257+19G>T		intron	N/A	ENSP00000297440.6
	DNAAF5	ENST00000852634.1		c.1338+19G>T		intron	N/A	ENSP00000522693.1
	DNAAF5	ENST00000852633.1		c.1257+19G>T		intron	N/A	ENSP00000522692.1

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152202 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000126 AC: 26 AN: 206866 AF XY: 0.0000709

Gnomad AFR exome AF: 0.00193

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000514 AC: 72 AN: 1400592 Hom.: 0 Cov.: 25 AF XY: 0.0000447 AC XY: 31 AN XY: 692764

African (AFR) AF: 0.00182 AC: 59 AN: 32366

American (AMR) AF: 0.0000246 AC: 1 AN: 40576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24500

East Asian (EAS) AF: 0.00 AC: 0 AN: 38350

South Asian (SAS) AF: 0.00 AC: 0 AN: 82124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4818

European-Non Finnish (NFE) AF: 0.00000935 AC: 10 AN: 1069060

Other (OTH) AF: 0.0000346 AC: 2 AN: 57884

GnomAD4 genome AF: 0.000506 AC: 77 AN: 152320 Hom.: 0 Cov.: 35 AF XY: 0.000483 AC XY: 36 AN XY: 74480

African (AFR) AF: 0.00180 AC: 75 AN: 41580

American (AMR) AF: 0.000131 AC: 2 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000434 Hom.: 0

Bravo AF: 0.000559

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.38
PhyloP100		-0.18

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: rs371368276; hg19: chr7-794477;