rs691151

Variant names:

• chr17-78486350-A-G
• rs691151
• NM_173628.4:c.6975T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-78486350-A-G
• chr17-78486350-A-C
• chr17-78486350-A-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.6975T>C​(p.Ile2325Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,613,636 control chromosomes in the GnomAD database, including 348,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31534 hom., cov: 31)
  • Exomes 𝑓: 0.66 (317194 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.167
• Publications: 18 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=-0.62).
• BP6: Variant 17-78486350-A-G is Benign according to our data. Variant chr17-78486350-A-G is described in ClinVar as Benign. ClinVar VariationId is 402681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.167 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.731 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.6975T>C	p.Ile2325Ile	synonymous	Exon 45 of 81	NP_775899.3	Q9UFH2-1
	DNAH17-AS1	NR_102401.1		n.253+1188A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.6975T>C	p.Ile2325Ile	synonymous	Exon 45 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17	ENST00000586052.5	TSL:5	n.354T>C		non_coding_transcript_exon	Exon 3 of 35
	DNAH17-AS1	ENST00000663269.1		n.708A>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97332 AN: 151926 Hom.: 31501 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.675

GnomAD2 exomes AF: 0.675 AC: 168244 AN: 249176 AF XY: 0.675

Gnomad AFR exome AF: 0.573

Gnomad AMR exome AF: 0.810

Gnomad ASJ exome AF: 0.699

Gnomad EAS exome AF: 0.600

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.660

Gnomad OTH exome AF: 0.674

GnomAD4 exome AF: 0.657 AC: 960642 AN: 1461592 Hom.: 317194 Cov.: 86 AF XY: 0.659 AC XY: 478961 AN XY: 727078

African (AFR) AF: 0.575 AC: 19245 AN: 33478

American (AMR) AF: 0.801 AC: 35834 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 18125 AN: 26136

East Asian (EAS) AF: 0.596 AC: 23677 AN: 39700

South Asian (SAS) AF: 0.727 AC: 62676 AN: 86254

European-Finnish (FIN) AF: 0.585 AC: 31219 AN: 53332

Middle Eastern (MID) AF: 0.695 AC: 4010 AN: 5768

European-Non Finnish (NFE) AF: 0.653 AC: 725963 AN: 1111832

Other (OTH) AF: 0.661 AC: 39893 AN: 60374

GnomAD4 genome AF: 0.641 AC: 97412 AN: 152044 Hom.: 31534 Cov.: 31 AF XY: 0.641 AC XY: 47602 AN XY: 74308

African (AFR) AF: 0.576 AC: 23857 AN: 41450

American (AMR) AF: 0.742 AC: 11354 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2439 AN: 3472

East Asian (EAS) AF: 0.595 AC: 3069 AN: 5158

South Asian (SAS) AF: 0.721 AC: 3477 AN: 4820

European-Finnish (FIN) AF: 0.592 AC: 6256 AN: 10564

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44707 AN: 67968

Other (OTH) AF: 0.671 AC: 1419 AN: 2116

Alfa AF: 0.649 Hom.: 24239

Bravo AF: 0.649

Asia WGS AF: 0.706 AC: 2455 AN: 3478

EpiCase AF: 0.669

EpiControl AF: 0.666

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	-0.62
CADD	Benign	7.9
DANN	Benign	0.65
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs691151; hg19: chr17-76482432; COSMIC: COSV67755106;