NM_173628.4:c.7422G>C

Variant names:

• chr17-78485611-C-G
• rs11872051
• NM_173628.4:c.7422G>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_173628.4(DNAH17):​c.7422G>C​(p.Thr2474Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 1,613,232 control chromosomes in the GnomAD database, including 356,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32175 hom., cov: 31)
  • Exomes 𝑓: 0.67 (324182 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.15
• Publications: 17 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=-0.82).
• BP6: Variant 17-78485611-C-G is Benign according to our data. Variant chr17-78485611-C-G is described in ClinVar as Benign. ClinVar VariationId is 402680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.711 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.7422G>C	p.Thr2474Thr	synonymous	Exon 47 of 81	NP_775899.3	Q9UFH2-1
	DNAH17-AS1	NR_102401.1		n.253+449C>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.7422G>C	p.Thr2474Thr	synonymous	Exon 47 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17	ENST00000586052.5	TSL:5	n.801G>C		non_coding_transcript_exon	Exon 5 of 35
	DNAH17-AS1	ENST00000588565.5	TSL:2	n.209+521C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98306 AN: 151872 Hom.: 32155 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.667

GnomAD2 exomes AF: 0.676 AC: 167640 AN: 248154 AF XY: 0.675

Gnomad AFR exome AF: 0.572

Gnomad AMR exome AF: 0.762

Gnomad ASJ exome AF: 0.677

Gnomad EAS exome AF: 0.582

Gnomad FIN exome AF: 0.671

Gnomad NFE exome AF: 0.671

Gnomad OTH exome AF: 0.677

GnomAD4 exome AF: 0.665 AC: 971862 AN: 1461242 Hom.: 324182 Cov.: 71 AF XY: 0.666 AC XY: 483780 AN XY: 726886

African (AFR) AF: 0.570 AC: 19072 AN: 33466

American (AMR) AF: 0.754 AC: 33670 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 17577 AN: 26122

East Asian (EAS) AF: 0.574 AC: 22754 AN: 39674

South Asian (SAS) AF: 0.703 AC: 60618 AN: 86202

European-Finnish (FIN) AF: 0.671 AC: 35801 AN: 53368

Middle Eastern (MID) AF: 0.674 AC: 3886 AN: 5768

European-Non Finnish (NFE) AF: 0.665 AC: 738720 AN: 1111632

Other (OTH) AF: 0.659 AC: 39764 AN: 60354

GnomAD4 genome AF: 0.647 AC: 98375 AN: 151990 Hom.: 32175 Cov.: 31 AF XY: 0.649 AC XY: 48252 AN XY: 74300

African (AFR) AF: 0.574 AC: 23786 AN: 41440

American (AMR) AF: 0.723 AC: 11042 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2385 AN: 3470

East Asian (EAS) AF: 0.587 AC: 3022 AN: 5150

South Asian (SAS) AF: 0.691 AC: 3328 AN: 4814

European-Finnish (FIN) AF: 0.678 AC: 7168 AN: 10568

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45433 AN: 67964

Other (OTH) AF: 0.670 AC: 1410 AN: 2104

Alfa AF: 0.642 Hom.: 8315

Bravo AF: 0.647

EpiCase AF: 0.678

EpiControl AF: 0.679

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	-0.82
CADD	Benign	0.012
DANN	Benign	0.67
PhyloP100		-4.1
Mutation Taster		=89/11	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: rs11872051; hg19: chr17-76481693; COSMIC: COSV67755611;