5-13886135-CAAAAAAAAAA-CAAAAAAAAA

Variant names:

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

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.2578-7delT 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 0.12 (817 hom., cov: 0)
  • Exomes 𝑓: 0.14 (142 hom.)
• Consequence: DNAH5 NM_001369.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• 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-CA-C is Benign according to our data. Variant chr5-13886135-CA-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 414363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 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.2578-7delT		splice_region intron	N/A	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.118-10435delA		intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.123 AC: 15189 AN: 123680 Hom.: 818 Cov.: 0

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.0591

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0827

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.102 AC: 6270 AN: 61536 AF XY: 0.0994

Gnomad AFR exome AF: 0.0968

Gnomad AMR exome AF: 0.0795

Gnomad ASJ exome AF: 0.0896

Gnomad EAS exome AF: 0.168

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.145 AC: 170185 AN: 1175852 Hom.: 142 Cov.: 0 AF XY: 0.142 AC XY: 82622 AN XY: 580464

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

African (AFR) AF: 0.0974 AC: 2516 AN: 25824

American (AMR) AF: 0.0729 AC: 1920 AN: 26330

Ashkenazi Jewish (ASJ) AF: 0.0970 AC: 1954 AN: 20154

East Asian (EAS) AF: 0.175 AC: 5514 AN: 31584

South Asian (SAS) AF: 0.0881 AC: 5456 AN: 61902

European-Finnish (FIN) AF: 0.179 AC: 5329 AN: 29832

Middle Eastern (MID) AF: 0.112 AC: 388 AN: 3454

European-Non Finnish (NFE) AF: 0.151 AC: 140464 AN: 927646

Other (OTH) AF: 0.135 AC: 6644 AN: 49126

⚠️ 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: 0.123 AC: 15190 AN: 123658 Hom.: 817 Cov.: 0 AF XY: 0.121 AC XY: 7092 AN XY: 58598

African (AFR) AF: 0.0795 AC: 2682 AN: 33756

American (AMR) AF: 0.0813 AC: 979 AN: 12038

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 210 AN: 3010

East Asian (EAS) AF: 0.121 AC: 433 AN: 3584

South Asian (SAS) AF: 0.0767 AC: 295 AN: 3844

European-Finnish (FIN) AF: 0.218 AC: 1301 AN: 5958

Middle Eastern (MID) AF: 0.0812 AC: 19 AN: 234

European-Non Finnish (NFE) AF: 0.154 AC: 9053 AN: 58764

Other (OTH) AF: 0.103 AC: 170 AN: 1658

Alfa AF: 0.0444 Hom.: 15

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs71600031;

hg19: chr5-13886244;

COSMIC: COSV54201919;