chr17-78561780-T-C

Variant names:

• chr17-78561780-T-C
• rs894966
• NM_173628.4:c.1770A>G

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.1770A>G​(p.Lys590Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 1,613,294 control chromosomes in the GnomAD database, including 735,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68168 hom., cov: 32)
  • Exomes 𝑓: 0.96 (667207 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.538
• Publications: 13 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 Gene-Disease associations (from GenCC):

• spermatogenic failure 39

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 17-78561780-T-C is Benign according to our data. Variant chr17-78561780-T-C is described in ClinVar as Benign. ClinVar VariationId is 402701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.538 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.955 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.1770A>G	p.Lys590Lys	synonymous	Exon 12 of 81	NP_775899.3	Q9UFH2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.1770A>G	p.Lys590Lys	synonymous	Exon 12 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17	ENST00000589793.1	TSL:2	n.982A>G		non_coding_transcript_exon	Exon 8 of 13

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143946 AN: 152158 Hom.: 68131 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.946

GnomAD2 exomes AF: 0.946 AC: 235710 AN: 249200 AF XY: 0.944

Gnomad AFR exome AF: 0.937

Gnomad AMR exome AF: 0.968

Gnomad ASJ exome AF: 0.936

Gnomad EAS exome AF: 0.911

Gnomad FIN exome AF: 0.899

Gnomad NFE exome AF: 0.961

Gnomad OTH exome AF: 0.951

GnomAD4 exome AF: 0.955 AC: 1395954 AN: 1461018 Hom.: 667207 Cov.: 71 AF XY: 0.954 AC XY: 693336 AN XY: 726732

African (AFR) AF: 0.936 AC: 31328 AN: 33468

American (AMR) AF: 0.964 AC: 43000 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 24422 AN: 26104

East Asian (EAS) AF: 0.912 AC: 36179 AN: 39670

South Asian (SAS) AF: 0.928 AC: 79903 AN: 86114

European-Finnish (FIN) AF: 0.904 AC: 48221 AN: 53322

Middle Eastern (MID) AF: 0.932 AC: 5374 AN: 5768

European-Non Finnish (NFE) AF: 0.963 AC: 1069971 AN: 1111596

Other (OTH) AF: 0.954 AC: 57556 AN: 60354

GnomAD4 genome AF: 0.946 AC: 144042 AN: 152276 Hom.: 68168 Cov.: 32 AF XY: 0.942 AC XY: 70164 AN XY: 74468

African (AFR) AF: 0.937 AC: 38947 AN: 41550

American (AMR) AF: 0.953 AC: 14581 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3258 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4730 AN: 5174

South Asian (SAS) AF: 0.930 AC: 4488 AN: 4824

European-Finnish (FIN) AF: 0.892 AC: 9472 AN: 10616

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.962 AC: 65409 AN: 68024

Other (OTH) AF: 0.942 AC: 1988 AN: 2110

Alfa AF: 0.955 Hom.: 30049

Bravo AF: 0.952

Asia WGS AF: 0.926 AC: 3221 AN: 3478

EpiCase AF: 0.961

EpiControl AF: 0.959

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	-0.58
CADD	Benign	7.6
DANN	Benign	0.62
PhyloP100		0.54
Mutation Taster		=98/2	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: rs894966; hg19: chr17-76557862; COSMIC: COSV67758972;