NM_001206927.2:c.9859+19_9859+23delAATGG

Variant names:

• chr6-38911592-AGGAAT-A
• rs878854276
• NM_001206927.2:c.9859+19_9859+23delAATGG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001206927.2(DNAH8):​c.9859+19_9859+23delAATGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000679 in 1,554,786 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (11 hom.)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

DNAH8-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 6-38911592-AGGAAT-A is Benign according to our data. Variant chr6-38911592-AGGAAT-A is described in ClinVar as Benign. ClinVar VariationId is 238660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. 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
	DNAH8	NM_001206927.2	MANE Select	c.9859+19_9859+23delAATGG		intron	N/A	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.9208+19_9208+23delAATGG		intron	N/A	NP_001362.2	Q96JB1-1
	DNAH8-AS1	NR_038401.1		n.783-3760_783-3756delATTCC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.9859+7_9859+11delGGAAT		splice_region intron	N/A	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000359357.7	TSL:2	c.9208+7_9208+11delGGAAT		splice_region intron	N/A	ENSP00000352312.3	Q96JB1-1
	DNAH8	ENST00000449981.6	TSL:5	c.9859+7_9859+11delGGAAT		splice_region intron	N/A	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes AF: 0.000789 AC: 120 AN: 152096 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00137 AC: 340 AN: 247718 AF XY: 0.00125

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000675

Gnomad ASJ exome AF: 0.0267

Gnomad EAS exome AF: 0.0000549

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000286

Gnomad OTH exome AF: 0.00250

GnomAD4 exome AF: 0.000667 AC: 936 AN: 1402572 Hom.: 11 AF XY: 0.000660 AC XY: 463 AN XY: 701238

African (AFR) AF: 0.0000310 AC: 1 AN: 32266

American (AMR) AF: 0.000583 AC: 26 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.0246 AC: 633 AN: 25750

East Asian (EAS) AF: 0.000229 AC: 9 AN: 39346

South Asian (SAS) AF: 0.0000589 AC: 5 AN: 84846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5628

European-Non Finnish (NFE) AF: 0.000163 AC: 173 AN: 1058378

Other (OTH) AF: 0.00151 AC: 88 AN: 58424

GnomAD4 genome AF: 0.000788 AC: 120 AN: 152214 Hom.: 1 Cov.: 32 AF XY: 0.000605 AC XY: 45 AN XY: 74430

African (AFR) AF: 0.0000723 AC: 3 AN: 41466

American (AMR) AF: 0.000523 AC: 8 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68024

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00382 Hom.: 1

Bravo AF: 0.000820

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs878854276; hg19: chr6-38879368;