NM_001206927.2:c.13054-17T>C

Variant names:

• chr6-38989995-T-C
• rs3737095
• NM_001206927.2:c.13054-17T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001206927.2(DNAH8):​c.13054-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,483,332 control chromosomes in the GnomAD database, including 134,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12544 hom., cov: 32)
  • Exomes 𝑓: 0.42 (121985 hom.)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.48
• Publications: 6 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 Gene-Disease associations (from GenCC):

• spermatogenic failure 46

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• spermatogenic failure 5

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-38989995-T-C is Benign according to our data. Variant chr6-38989995-T-C is described in ClinVar as Benign. ClinVar VariationId is 257628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

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.13054-17T>C		intron	N/A	NP_001193856.1
	DNAH8	NM_001371.4		c.12403-17T>C		intron	N/A	NP_001362.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.13054-17T>C		intron	N/A	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.12403-17T>C		intron	N/A	ENSP00000352312.3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60697 AN: 151868 Hom.: 12533 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.381 AC: 79008 AN: 207216 AF XY: 0.383

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.373

Gnomad EAS exome AF: 0.238

Gnomad FIN exome AF: 0.432

Gnomad NFE exome AF: 0.442

Gnomad OTH exome AF: 0.405

GnomAD4 exome AF: 0.422 AC: 562276 AN: 1331346 Hom.: 121985 Cov.: 20 AF XY: 0.420 AC XY: 278063 AN XY: 662422

African (AFR) AF: 0.313 AC: 9205 AN: 29384

American (AMR) AF: 0.323 AC: 10755 AN: 33282

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 8840 AN: 23010

East Asian (EAS) AF: 0.233 AC: 8818 AN: 37848

South Asian (SAS) AF: 0.288 AC: 21661 AN: 75092

European-Finnish (FIN) AF: 0.441 AC: 22758 AN: 51548

Middle Eastern (MID) AF: 0.438 AC: 2367 AN: 5402

European-Non Finnish (NFE) AF: 0.446 AC: 454775 AN: 1020276

Other (OTH) AF: 0.416 AC: 23097 AN: 55504

GnomAD4 genome AF: 0.400 AC: 60742 AN: 151986 Hom.: 12544 Cov.: 32 AF XY: 0.396 AC XY: 29446 AN XY: 74304

African (AFR) AF: 0.336 AC: 13919 AN: 41438

American (AMR) AF: 0.380 AC: 5807 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5176

South Asian (SAS) AF: 0.296 AC: 1423 AN: 4812

European-Finnish (FIN) AF: 0.445 AC: 4689 AN: 10546

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.454 AC: 30851 AN: 67950

Other (OTH) AF: 0.400 AC: 843 AN: 2110

Alfa AF: 0.411 Hom.: 2961

Bravo AF: 0.392

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3737095; hg19: chr6-38957771; COSMIC: COSV59469826;