rs1678690

Variant names:

• chr6-38814090-C-A
• rs1678690
• NM_001206927.2:c.3294C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-38814090-C-A
• chr6-38814090-C-G
• chr6-38814090-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS1

The NM_001206927.2(DNAH8):​c.3294C>A​(p.Ser1098Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000368 in 1,585,198 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. S1098S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0570
• Publications: 10 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 6-38814090-C-A is Benign according to our data. Variant chr6-38814090-C-A is described in ClinVar as Benign. ClinVar VariationId is 414423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.057 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00186 (283/152036) while in subpopulation AFR AF = 0.00653 (271/41476). AF 95% confidence interval is 0.00589. There are 0 homozygotes in GnomAd4. There are 121 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.3294C>A	p.Ser1098Ser	synonymous	Exon 25 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.2643C>A	p.Ser881Ser	synonymous	Exon 24 of 92	NP_001362.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.3294C>A	p.Ser1098Ser	synonymous	Exon 25 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.2643C>A	p.Ser881Ser	synonymous	Exon 23 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.3294C>A	p.Ser1098Ser	synonymous	Exon 24 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 282 AN: 151918 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00653

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000572 AC: 142 AN: 248150 AF XY: 0.000395

Gnomad AFR exome AF: 0.00756

Gnomad AMR exome AF: 0.000388

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000210 AC: 301 AN: 1433162 Hom.: 1 Cov.: 29 AF XY: 0.000167 AC XY: 119 AN XY: 714540

African (AFR) AF: 0.00741 AC: 244 AN: 32946

American (AMR) AF: 0.000364 AC: 16 AN: 44004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.0000508 AC: 2 AN: 39334

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.000873 AC: 5 AN: 5728

European-Non Finnish (NFE) AF: 0.00000827 AC: 9 AN: 1087614

Other (OTH) AF: 0.000388 AC: 23 AN: 59318

GnomAD4 genome AF: 0.00186 AC: 283 AN: 152036 Hom.: 0 Cov.: 32 AF XY: 0.00163 AC XY: 121 AN XY: 74298

African (AFR) AF: 0.00653 AC: 271 AN: 41476

American (AMR) AF: 0.000458 AC: 7 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67968

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.0000935 Hom.: 1463

EpiCase AF: 0.00

EpiControl AF: 0.0000594

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
BayesDel_noAF	Benign	-0.27
CADD	Benign	7.2
DANN	Benign	0.72
PhyloP100		0.057
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs1678690; hg19: chr6-38781866;