rs606944

Variant names:

• chr17-78495046-G-C
• rs606944
• NM_173628.4:c.5955C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-78495046-G-C
• chr17-78495046-G-A
• chr17-78495046-G-T

Variant summary

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

The NM_173628.4(DNAH17):​c.5955C>G​(p.Leu1985Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,610,586 control chromosomes in the GnomAD database, including 567,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58070 hom., cov: 34)
  • Exomes 𝑓: 0.83 (509514 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.916
• Publications: 14 publications found

Genes affected

DNAH17 (HGNC:2946): (dynein axonemal heavy chain 17) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. DNAH17 is a heavy chain associated with axonemal dynein (Milisav and Affara, 1998 [PubMed 9545504]).[supplied by OMIM, Mar 2008]

DNAH17-AS1 (HGNC:48594): (DNAH17 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-78495046-G-C is Benign according to our data. Variant chr17-78495046-G-C is described in ClinVar as Benign. ClinVar VariationId is 402683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.916 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173628.4. 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
	DNAH17	NM_173628.4	MANE Select	c.5955C>G	p.Leu1985Leu	synonymous	Exon 39 of 81	NP_775899.3	Q9UFH2-1
	DNAH17-AS1	NR_102401.1		n.769+849G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.5955C>G	p.Leu1985Leu	synonymous	Exon 39 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17-AS1	ENST00000591373.2	TSL:5	n.769+849G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132271 AN: 151950 Hom.: 58007 Cov.: 34

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.876

GnomAD2 exomes AF: 0.863 AC: 210518 AN: 243820 AF XY: 0.861

Gnomad AFR exome AF: 0.971

Gnomad AMR exome AF: 0.916

Gnomad ASJ exome AF: 0.849

Gnomad EAS exome AF: 0.977

Gnomad FIN exome AF: 0.808

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.845

GnomAD4 exome AF: 0.834 AC: 1217101 AN: 1458518 Hom.: 509514 Cov.: 66 AF XY: 0.836 AC XY: 606050 AN XY: 725304

African (AFR) AF: 0.975 AC: 32600 AN: 33434

American (AMR) AF: 0.913 AC: 40494 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 22105 AN: 26044

East Asian (EAS) AF: 0.988 AC: 39158 AN: 39642

South Asian (SAS) AF: 0.926 AC: 79483 AN: 85802

European-Finnish (FIN) AF: 0.810 AC: 42898 AN: 52942

Middle Eastern (MID) AF: 0.860 AC: 4956 AN: 5762

European-Non Finnish (NFE) AF: 0.814 AC: 904060 AN: 1110292

Other (OTH) AF: 0.852 AC: 51347 AN: 60264

GnomAD4 genome AF: 0.871 AC: 132394 AN: 152068 Hom.: 58070 Cov.: 34 AF XY: 0.873 AC XY: 64872 AN XY: 74298

African (AFR) AF: 0.968 AC: 40211 AN: 41546

American (AMR) AF: 0.880 AC: 13459 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2966 AN: 3466

East Asian (EAS) AF: 0.978 AC: 5063 AN: 5178

South Asian (SAS) AF: 0.932 AC: 4500 AN: 4826

European-Finnish (FIN) AF: 0.808 AC: 8516 AN: 10544

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54833 AN: 67908

Other (OTH) AF: 0.878 AC: 1853 AN: 2110

Alfa AF: 0.816 Hom.: 13045

Bravo AF: 0.881

Asia WGS AF: 0.965 AC: 3357 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DNAH17-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.2
DANN	Benign	0.81
PhyloP100		0.92
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: rs606944; hg19: chr17-76491128; COSMIC: COSV67758966; COSMIC: COSV67758966;