chr17-78486012-G-T

Variant names:

• chr17-78486012-G-T
• rs1032525270
• NM_173628.4:c.7223C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173628.4(DNAH17):​c.7223C>A​(p.Pro2408His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2408R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAH17 NM_173628.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.7223C>A	p.Pro2408His	missense	Exon 46 of 81	NP_775899.3	Q9UFH2-1
	DNAH17-AS1	NR_102401.1		n.253+850G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.7223C>A	p.Pro2408His	missense	Exon 46 of 81	ENSP00000374490.6	Q9UFH2-1
	DNAH17	ENST00000586052.5	TSL:5	n.602C>A		non_coding_transcript_exon	Exon 4 of 35
	DNAH17-AS1	ENST00000663269.1		n.370G>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461614 Hom.: 0 Cov.: 70 AF XY: 0.00000138 AC XY: 1 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111868

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.65	T
PhyloP100		2.7
PrimateAI	Benign	0.48	T
REVEL	Benign	0.21
Vest4		0.63
MVP		0.30
ClinPred		0.84	D
GERP RS		4.4
Varity_R		0.21
gMVP		0.52

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: rs1032525270; hg19: chr17-76482094;