rs6554817

Variant names:

• chr5-13820547-G-A
• rs6554817
• NM_001369.3:c.6688-48C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13820547-G-A
• chr5-13820547-G-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.6688-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,604,744 control chromosomes in the GnomAD database, including 36,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3387 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33466 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.60
• Publications: 4 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: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 5-13820547-G-A is Benign according to our data. Variant chr5-13820547-G-A is described in ClinVar as Benign. ClinVar VariationId is 258054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 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.6688-48C>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.6688-48C>T		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.6643-48C>T		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000683090.1		n.1619-48C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31017 AN: 151976 Hom.: 3389 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.213 AC: 52560 AN: 246692 AF XY: 0.210

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.540

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.207 AC: 301275 AN: 1452652 Hom.: 33466 Cov.: 30 AF XY: 0.206 AC XY: 148915 AN XY: 723160

African (AFR) AF: 0.184 AC: 6140 AN: 33332

American (AMR) AF: 0.164 AC: 7313 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3895 AN: 26098

East Asian (EAS) AF: 0.487 AC: 19293 AN: 39640

South Asian (SAS) AF: 0.165 AC: 14210 AN: 86090

European-Finnish (FIN) AF: 0.195 AC: 9712 AN: 49926

Middle Eastern (MID) AF: 0.125 AC: 610 AN: 4890

European-Non Finnish (NFE) AF: 0.205 AC: 227684 AN: 1107954

Other (OTH) AF: 0.207 AC: 12418 AN: 60058

GnomAD4 genome AF: 0.204 AC: 31028 AN: 152092 Hom.: 3387 Cov.: 32 AF XY: 0.202 AC XY: 15044 AN XY: 74332

African (AFR) AF: 0.184 AC: 7645 AN: 41502

American (AMR) AF: 0.173 AC: 2645 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 529 AN: 3470

East Asian (EAS) AF: 0.526 AC: 2716 AN: 5162

South Asian (SAS) AF: 0.181 AC: 872 AN: 4814

European-Finnish (FIN) AF: 0.191 AC: 2021 AN: 10584

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.204 AC: 13857 AN: 67964

Other (OTH) AF: 0.206 AC: 435 AN: 2108

Alfa AF: 0.198 Hom.: 581

Bravo AF: 0.207

Asia WGS AF: 0.303 AC: 1051 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.60
PhyloP100		-3.6
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: rs6554817; hg19: chr5-13820656;