rs6554813

Variant names:

• chr5-13762930-G-A
• rs6554813
• NM_001369.3:c.10102-29C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001369.3(DNAH5):​c.10102-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,587,034 control chromosomes in the GnomAD database, including 66,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.31 (7641 hom., cov: 33)
  • Exomes 𝑓: 0.28 (58997 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.327
• Publications: 7 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-13762930-G-A is Benign according to our data. Variant chr5-13762930-G-A is described in ClinVar as Benign. ClinVar VariationId is 257971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.423 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.10102-29C>T		intron	N/A	NP_001360.1	Q8TE73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.10102-29C>T		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.10057-29C>T		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000504001.3	TSL:5	n.610-29C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46581 AN: 151932 Hom.: 7624 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.280

GnomAD2 exomes AF: 0.297 AC: 73526 AN: 247876 AF XY: 0.301

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.0929

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.279 AC: 400613 AN: 1434982 Hom.: 58997 Cov.: 28 AF XY: 0.284 AC XY: 203151 AN XY: 715752

African (AFR) AF: 0.360 AC: 11870 AN: 32936

American (AMR) AF: 0.294 AC: 13094 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 5414 AN: 26004

East Asian (EAS) AF: 0.102 AC: 4027 AN: 39500

South Asian (SAS) AF: 0.431 AC: 36945 AN: 85646

European-Finnish (FIN) AF: 0.410 AC: 21285 AN: 51972

Middle Eastern (MID) AF: 0.224 AC: 1283 AN: 5722

European-Non Finnish (NFE) AF: 0.267 AC: 290310 AN: 1089102

Other (OTH) AF: 0.275 AC: 16385 AN: 59536

GnomAD4 genome AF: 0.307 AC: 46649 AN: 152052 Hom.: 7641 Cov.: 33 AF XY: 0.314 AC XY: 23308 AN XY: 74316

African (AFR) AF: 0.363 AC: 15042 AN: 41482

American (AMR) AF: 0.271 AC: 4150 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3466

East Asian (EAS) AF: 0.112 AC: 581 AN: 5182

South Asian (SAS) AF: 0.438 AC: 2110 AN: 4814

European-Finnish (FIN) AF: 0.442 AC: 4663 AN: 10542

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18582 AN: 67956

Other (OTH) AF: 0.283 AC: 597 AN: 2110

Alfa AF: 0.294 Hom.: 1616

Bravo AF: 0.290

Asia WGS AF: 0.324 AC: 1124 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia 3 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.6
DANN	Benign	0.72
PhyloP100		0.33
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs6554813; hg19: chr5-13763039;