5-13886135-CAAAAAAAAAA-CAAAAAAAAAAA

Variant names:

• chr5-13886135-C-CA
• rs71600031
• NM_001369.3:c.2578-7dupT

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.2578-7dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (65 hom., cov: 0)
  • Exomes 𝑓: 0.019 (8 hom.)
• Consequence: DNAH5 NM_001369.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0110
• 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-C-CA is Benign according to our data. Variant chr5-13886135-C-CA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1269037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0602 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.2578-7dupT		splice_region intron	N/A	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.118-10435dupA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.2578-7_2578-6insT		splice_region intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.2533-7_2533-6insT		splice_region intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.254-10454_254-10453insA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 2583 AN: 123802 Hom.: 65 Cov.: 0

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00532

Gnomad EAS AF: 0.0109

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.000835

Gnomad MID AF: 0.0273

Gnomad NFE AF: 0.00311

Gnomad OTH AF: 0.0218

GnomAD2 exomes AF: 0.0376 AC: 2316 AN: 61536 AF XY: 0.0361

Gnomad AFR exome AF: 0.0531

Gnomad AMR exome AF: 0.0362

Gnomad ASJ exome AF: 0.0308

Gnomad EAS exome AF: 0.0975

Gnomad FIN exome AF: 0.0183

Gnomad NFE exome AF: 0.0312

Gnomad OTH exome AF: 0.0319

GnomAD4 exome AF: 0.0188 AC: 22720 AN: 1205682 Hom.: 8 Cov.: 0 AF XY: 0.0188 AC XY: 11187 AN XY: 595948

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

African (AFR) AF: 0.0428 AC: 1120 AN: 26198

American (AMR) AF: 0.0253 AC: 679 AN: 26816

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 456 AN: 20550

East Asian (EAS) AF: 0.0436 AC: 1400 AN: 32102

South Asian (SAS) AF: 0.0240 AC: 1545 AN: 64432

European-Finnish (FIN) AF: 0.0162 AC: 503 AN: 30982

Middle Eastern (MID) AF: 0.0231 AC: 81 AN: 3502

European-Non Finnish (NFE) AF: 0.0166 AC: 15824 AN: 950776

Other (OTH) AF: 0.0221 AC: 1112 AN: 50324

⚠️ 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: 0.0209 AC: 2583 AN: 123780 Hom.: 65 Cov.: 0 AF XY: 0.0206 AC XY: 1211 AN XY: 58676

African (AFR) AF: 0.0624 AC: 2108 AN: 33760

American (AMR) AF: 0.0105 AC: 126 AN: 12040

Ashkenazi Jewish (ASJ) AF: 0.00532 AC: 16 AN: 3010

East Asian (EAS) AF: 0.0109 AC: 39 AN: 3582

South Asian (SAS) AF: 0.0164 AC: 63 AN: 3852

European-Finnish (FIN) AF: 0.000835 AC: 5 AN: 5988

Middle Eastern (MID) AF: 0.0297 AC: 7 AN: 236

European-Non Finnish (NFE) AF: 0.00311 AC: 183 AN: 58842

Other (OTH) AF: 0.0217 AC: 36 AN: 1658

Alfa AF: 0.0161 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		0.011
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: rs71600031; hg19: chr5-13886244;