6-38911592-AGGAAT-A

Position:

• chr6-38911592-AGGAAT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001206927.2(DNAH8):​c.9859+19_9859+23del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000679 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 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19

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:):

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 238660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.9859+19_9859+23del		splice_region_variant, intron_variant		ENST00000327475.11	NP_001193856.1
DNAH8-AS1	NR_038401.1	n.783-3760_783-3756del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.9859+19_9859+23del		splice_region_variant, intron_variant		5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7	c.9208+19_9208+23del		splice_region_variant, intron_variant		2		ENSP00000352312	A2
DNAH8	ENST00000449981.6	c.9859+19_9859+23del		splice_region_variant, intron_variant		5		ENSP00000415331

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

GnomAD3 exomes AF: 0.00137 AC: 340 AN: 247718 Hom.: 6 AF XY: 0.00125 AC XY: 168 AN XY: 133936

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 SAS exome AF: 0.00

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

Gnomad4 AFR exome AF: 0.0000310

Gnomad4 AMR exome AF: 0.000583

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.000229

Gnomad4 SAS exome AF: 0.0000589

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000163

Gnomad4 OTH exome AF: 0.00151

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

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00382 Hom.: 1

Bravo AF: 0.000820

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs878854276; hg19: chr6-38879368;