chr5-13886135-CAAAAA-C

Variant names:

• chr5-13886135-CAAAAA-C
• rs71600031
• NM_001369.3:c.2578-11_2578-7delTTTTT

Variant summary

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

The NM_001369.3(DNAH5):​c.2578-11_2578-7delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00613 in 1,330,360 control chromosomes in the GnomAD database, including 63 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (53 hom., cov: 0)
  • Exomes 𝑓: 0.0051 (10 hom.)
• Consequence: DNAH5 NM_001369.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.52
• Publications: 2 publications found

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH5-AS1 (HGNC:40187):

ACMG classification

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

• BP6: Variant 5-13886135-CAAAAA-C is Benign according to our data. Variant chr5-13886135-CAAAAA-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1283044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.2578-11_2578-7delTTTTT		splice_region intron	N/A	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.118-10439_118-10435delAAAAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.2578-11_2578-7delTTTTT		splice_region intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.2533-11_2533-7delTTTTT		splice_region intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.254-10453_254-10449delAAAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 1989 AN: 123856 Hom.: 53 Cov.: 0

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00299

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0117

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0133

GnomAD2 exomes AF: 0.00998 AC: 614 AN: 61536 AF XY: 0.00914

Gnomad AFR exome AF: 0.0608

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.00562

Gnomad EAS exome AF: 0.000607

Gnomad FIN exome AF: 0.00577

Gnomad NFE exome AF: 0.00413

Gnomad OTH exome AF: 0.00811

GnomAD4 exome AF: 0.00511 AC: 6163 AN: 1206528 Hom.: 10 AF XY: 0.00476 AC XY: 2838 AN XY: 596626

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0573 AC: 1519 AN: 26492

American (AMR) AF: 0.00918 AC: 248 AN: 27004

Ashkenazi Jewish (ASJ) AF: 0.00683 AC: 141 AN: 20648

East Asian (EAS) AF: 0.00134 AC: 44 AN: 32790

South Asian (SAS) AF: 0.00319 AC: 207 AN: 64904

European-Finnish (FIN) AF: 0.00361 AC: 112 AN: 30994

Middle Eastern (MID) AF: 0.00795 AC: 28 AN: 3524

European-Non Finnish (NFE) AF: 0.00361 AC: 3429 AN: 949816

Other (OTH) AF: 0.00864 AC: 435 AN: 50356

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0161 AC: 1995 AN: 123832 Hom.: 53 Cov.: 0 AF XY: 0.0162 AC XY: 950 AN XY: 58702

African (AFR) AF: 0.0540 AC: 1826 AN: 33786

American (AMR) AF: 0.0101 AC: 122 AN: 12042

Ashkenazi Jewish (ASJ) AF: 0.00299 AC: 9 AN: 3012

East Asian (EAS) AF: 0.00 AC: 0 AN: 3584

South Asian (SAS) AF: 0.00 AC: 0 AN: 3852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5982

Middle Eastern (MID) AF: 0.0127 AC: 3 AN: 236

European-Non Finnish (NFE) AF: 0.000221 AC: 13 AN: 58864

Other (OTH) AF: 0.0132 AC: 22 AN: 1662

Alfa AF: 0.00 Hom.: 15

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71600031; hg19: chr5-13886244;