rs2271613

Variant names:

• chr17-78427016-G-A
• rs2271613
• NM_173628.4:c.12681C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78427016-G-A
• chr17-78427016-G-C
• chr17-78427016-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.12681C>T​(p.Tyr4227Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 1,607,814 control chromosomes in the GnomAD database, including 423,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (34421 hom., cov: 32)
  • Exomes 𝑓: 0.73 (388778 hom.)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.423
• Publications: 29 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=-0.54).
• BP6: Variant 17-78427016-G-A is Benign according to our data. Variant chr17-78427016-G-A is described in ClinVar as Benign. ClinVar VariationId is 402672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.423 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	NM_173628.4	MANE Select	c.12681C>T	p.Tyr4227Tyr	synonymous	Exon 78 of 81	NP_775899.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.12681C>T	p.Tyr4227Tyr	synonymous	Exon 78 of 81	ENSP00000374490.6
	DNAH17	ENST00000586052.5	TSL:5	n.5842C>T		non_coding_transcript_exon	Exon 32 of 35
	DNAH17	ENST00000586850.1	TSL:3	n.213C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99384 AN: 151968 Hom.: 34409 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.662

GnomAD2 exomes AF: 0.738 AC: 178120 AN: 241370 AF XY: 0.737

Gnomad AFR exome AF: 0.408

Gnomad AMR exome AF: 0.816

Gnomad ASJ exome AF: 0.643

Gnomad EAS exome AF: 0.933

Gnomad FIN exome AF: 0.823

Gnomad NFE exome AF: 0.726

Gnomad OTH exome AF: 0.710

GnomAD4 exome AF: 0.727 AC: 1058665 AN: 1455728 Hom.: 388778 Cov.: 59 AF XY: 0.727 AC XY: 526203 AN XY: 723510

African (AFR) AF: 0.403 AC: 13449 AN: 33386

American (AMR) AF: 0.808 AC: 35380 AN: 43806

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 16600 AN: 25926

East Asian (EAS) AF: 0.950 AC: 37573 AN: 39560

South Asian (SAS) AF: 0.720 AC: 61259 AN: 85076

European-Finnish (FIN) AF: 0.821 AC: 43450 AN: 52948

Middle Eastern (MID) AF: 0.619 AC: 3568 AN: 5764

European-Non Finnish (NFE) AF: 0.725 AC: 804264 AN: 1109104

Other (OTH) AF: 0.717 AC: 43122 AN: 60158

GnomAD4 genome AF: 0.654 AC: 99423 AN: 152086 Hom.: 34421 Cov.: 32 AF XY: 0.663 AC XY: 49325 AN XY: 74350

African (AFR) AF: 0.416 AC: 17235 AN: 41470

American (AMR) AF: 0.740 AC: 11316 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2219 AN: 3472

East Asian (EAS) AF: 0.937 AC: 4848 AN: 5176

South Asian (SAS) AF: 0.732 AC: 3535 AN: 4826

European-Finnish (FIN) AF: 0.831 AC: 8801 AN: 10590

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49164 AN: 67948

Other (OTH) AF: 0.663 AC: 1401 AN: 2112

Alfa AF: 0.703 Hom.: 178874

Bravo AF: 0.638

Asia WGS AF: 0.809 AC: 2809 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.54
CADD	Benign	1.1
DANN	Benign	0.93
PhyloP100		-0.42
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: rs2271613; hg19: chr17-76423097; COSMIC: COSV53145495; COSMIC: COSV53145495;