chr5-13701247-T-C

Variant names:

• chr5-13701247-T-C
• rs10069041
• NM_001369.3:c.13491+37A>G

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.13491+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,620 control chromosomes in the GnomAD database, including 1,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (995 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (932 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.561
• Publications: 1 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=-0.59).
• BP6: Variant 5-13701247-T-C is Benign according to our data. Variant chr5-13701247-T-C is described in ClinVar as Benign. ClinVar VariationId is 258000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 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.13491+37A>G		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.13491+37A>G		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.13446+37A>G		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000683611.1		n.824+37A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9822 AN: 151918 Hom.: 990 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00935

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.0475

GnomAD2 exomes AF: 0.0201 AC: 5029 AN: 249922 AF XY: 0.0167

Gnomad AFR exome AF: 0.224

Gnomad AMR exome AF: 0.0172

Gnomad ASJ exome AF: 0.0114

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.00325

Gnomad OTH exome AF: 0.0168

GnomAD4 exome AF: 0.00877 AC: 12819 AN: 1461584 Hom.: 932 Cov.: 34 AF XY: 0.00824 AC XY: 5995 AN XY: 727128

African (AFR) AF: 0.221 AC: 7393 AN: 33454

American (AMR) AF: 0.0187 AC: 836 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0122 AC: 319 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0115 AC: 990 AN: 86250

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53416

Middle Eastern (MID) AF: 0.0501 AC: 289 AN: 5766

European-Non Finnish (NFE) AF: 0.00167 AC: 1862 AN: 1111760

Other (OTH) AF: 0.0186 AC: 1123 AN: 60386

GnomAD4 genome AF: 0.0648 AC: 9845 AN: 152036 Hom.: 995 Cov.: 32 AF XY: 0.0630 AC XY: 4681 AN XY: 74324

African (AFR) AF: 0.216 AC: 8961 AN: 41428

American (AMR) AF: 0.0312 AC: 476 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00915 AC: 44 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.00278 AC: 189 AN: 68000

Other (OTH) AF: 0.0470 AC: 99 AN: 2108

Alfa AF: 0.0521 Hom.: 160

Bravo AF: 0.0735

Asia WGS AF: 0.0200 AC: 72 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)
-	-	1	Primary ciliary dyskinesia 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		-0.56
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: rs10069041; hg19: chr5-13701356;