rs2289751

Variant names:

• chr17-78453423-G-A
• rs2289751
• NM_173628.4:c.10449C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78453423-G-A
• chr17-78453423-G-C
• chr17-78453423-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_173628.4(DNAH17):​c.10449C>T​(p.Thr3483Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T3483T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: DNAH17 NM_173628.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 16 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=-0.319 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH17	NM_173628.4	c.10449C>T	p.Thr3483Thr	synonymous_variant	Exon 65 of 81	ENST00000389840.7	NP_775899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH17	ENST00000389840.7	c.10449C>T	p.Thr3483Thr	synonymous_variant	Exon 65 of 81	5	NM_173628.4	ENSP00000374490.6
DNAH17	ENST00000586052.5	n.3734C>T		non_coding_transcript_exon_variant	Exon 20 of 35	5
DNAH17	ENST00000591369.5	n.2049C>T		non_coding_transcript_exon_variant	Exon 12 of 28	5		ENSP00000466150.1
DNAH17	ENST00000592152.1	n.796C>T		non_coding_transcript_exon_variant	Exon 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	5.3
DANN	Benign	0.69
PhyloP100		-0.32

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: rs2289751; hg19: chr17-76449505;