rs2896103

Variant names:

• chr5-13764310-G-A
• rs2896103
• NM_001369.3:c.10102-1409C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13764310-G-A
• chr5-13764310-G-C
• chr5-13764310-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369.3(DNAH5):​c.10102-1409C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,000 control chromosomes in the GnomAD database, including 7,624 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7624 hom., cov: 33)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• Publications: 9 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.10102-1409C>T		intron	N/A	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.10102-1409C>T		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.10057-1409C>T		intron	N/A	ENSP00000505288.1
	DNAH5	ENST00000504001.3	TSL:5	n.610-1409C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46508 AN: 151882 Hom.: 7604 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.278

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.306 AC: 46581 AN: 152000 Hom.: 7624 Cov.: 33 AF XY: 0.313 AC XY: 23278 AN XY: 74292

African (AFR) AF: 0.362 AC: 15008 AN: 41430

American (AMR) AF: 0.270 AC: 4123 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3468

East Asian (EAS) AF: 0.113 AC: 584 AN: 5186

South Asian (SAS) AF: 0.439 AC: 2113 AN: 4812

European-Finnish (FIN) AF: 0.442 AC: 4650 AN: 10526

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18588 AN: 67984

Other (OTH) AF: 0.281 AC: 593 AN: 2112

Alfa AF: 0.276 Hom.: 13441

Bravo AF: 0.289

Asia WGS AF: 0.324 AC: 1123 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		0.14
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: rs2896103; hg19: chr5-13764419;