rs1348689

Variant names:

• chr5-13829690-G-A
• rs1348689
• NM_001369.3:c.6264C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13829690-G-A
• chr5-13829690-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001369.3(DNAH5):​c.6264C>T​(p.Ala2088Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,612,658 control chromosomes in the GnomAD database, including 114,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A2088A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.40 (12283 hom., cov: 33)
  • Exomes 𝑓: 0.37 (101984 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.832
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-13829690-G-A is Benign according to our data. Variant chr5-13829690-G-A is described in ClinVar as Benign. ClinVar VariationId is 163145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.832 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 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.6264C>T	p.Ala2088Ala	synonymous	Exon 38 of 79	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.6264C>T	p.Ala2088Ala	synonymous	Exon 38 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.6219C>T	p.Ala2073Ala	synonymous	Exon 38 of 79	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000683090.1		n.1195C>T		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60495 AN: 151858 Hom.: 12267 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.385 AC: 96523 AN: 250998 AF XY: 0.379

Gnomad AFR exome AF: 0.464

Gnomad AMR exome AF: 0.373

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.624

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.381

GnomAD4 exome AF: 0.371 AC: 541740 AN: 1460680 Hom.: 101984 Cov.: 37 AF XY: 0.369 AC XY: 267886 AN XY: 726712

African (AFR) AF: 0.459 AC: 15365 AN: 33452

American (AMR) AF: 0.378 AC: 16884 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9392 AN: 26134

East Asian (EAS) AF: 0.562 AC: 22319 AN: 39690

South Asian (SAS) AF: 0.330 AC: 28419 AN: 86246

European-Finnish (FIN) AF: 0.328 AC: 17488 AN: 53396

Middle Eastern (MID) AF: 0.335 AC: 1933 AN: 5762

European-Non Finnish (NFE) AF: 0.366 AC: 407021 AN: 1110926

Other (OTH) AF: 0.380 AC: 22919 AN: 60364

GnomAD4 genome AF: 0.398 AC: 60548 AN: 151978 Hom.: 12283 Cov.: 33 AF XY: 0.396 AC XY: 29383 AN XY: 74278

African (AFR) AF: 0.461 AC: 19099 AN: 41420

American (AMR) AF: 0.383 AC: 5855 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3470

East Asian (EAS) AF: 0.610 AC: 3151 AN: 5166

South Asian (SAS) AF: 0.331 AC: 1590 AN: 4806

European-Finnish (FIN) AF: 0.317 AC: 3351 AN: 10556

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24884 AN: 67970

Other (OTH) AF: 0.397 AC: 837 AN: 2108

Alfa AF: 0.364 Hom.: 7318

Bravo AF: 0.411

Asia WGS AF: 0.454 AC: 1578 AN: 3478

EpiCase AF: 0.370

EpiControl AF: 0.364

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		-0.83
Mutation Taster		=71/29	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: rs1348689; hg19: chr5-13829799; COSMIC: COSV54225144;