chr17-78485764-C-CAGGGGAGGGA

Variant names:

• chr17-78485764-C-CAGGGGAGGGA
• rs200138898
• NM_173628.4:c.7276-17_7276-8dupTCCCTCCCCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_173628.4(DNAH17):​c.7276-17_7276-8dupTCCCTCCCCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,611,548 control chromosomes in the GnomAD database, including 305 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (187 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (118 hom.)
• Consequence: DNAH17 NM_173628.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0900
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 17-78485764-C-CAGGGGAGGGA is Benign according to our data. Variant chr17-78485764-C-CAGGGGAGGGA is described in ClinVar as Benign. ClinVar VariationId is 1282044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0888 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.7276-17_7276-8dupTCCCTCCCCT		splice_region intron	N/A	NP_775899.3	Q9UFH2-1
	DNAH17-AS1	NR_102401.1		n.253+613_253+622dupAGGGGAGGGA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.7276-8_7276-7insTCCCTCCCCT		splice_region intron	N/A	ENSP00000374490.6	Q9UFH2-1
	DNAH17	ENST00000586052.5	TSL:5	n.655-8_655-7insTCCCTCCCCT		splice_region intron	N/A
	DNAH17-AS1	ENST00000588565.5	TSL:2	n.209+674_209+675insAGGGGAGGGA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3987 AN: 151968 Hom.: 187 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00613 AC: 1520 AN: 247920 AF XY: 0.00469

Gnomad AFR exome AF: 0.0867

Gnomad AMR exome AF: 0.00421

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.000278

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000223

Gnomad OTH exome AF: 0.00299

GnomAD4 exome AF: 0.00214 AC: 3116 AN: 1459466 Hom.: 118 Cov.: 36 AF XY: 0.00182 AC XY: 1322 AN XY: 726004

African (AFR) AF: 0.0754 AC: 2444 AN: 32416

American (AMR) AF: 0.00493 AC: 220 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26060

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39680

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5758

European-Non Finnish (NFE) AF: 0.0000846 AC: 94 AN: 1111128

Other (OTH) AF: 0.00511 AC: 308 AN: 60248

GnomAD4 genome AF: 0.0262 AC: 3992 AN: 152082 Hom.: 187 Cov.: 32 AF XY: 0.0254 AC XY: 1891 AN XY: 74378

African (AFR) AF: 0.0913 AC: 3777 AN: 41390

American (AMR) AF: 0.00981 AC: 150 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68002

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.00434 Hom.: 10

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000356

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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200138898; hg19: chr17-76481846;