chr6-38776780-T-C

Variant names:

• chr6-38776780-T-C
• rs1738262
• NM_001206927.2:c.1962+829T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000327475.11(DNAH8):​c.1962+829T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 152,168 control chromosomes in the GnomAD database, including 1,292 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.096 (1292 hom., cov: 32)
• Consequence: DNAH8 ENST00000327475.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000327475.11. 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.1962+829T>C		intron	N/A	NP_001193856.1
	DNAH8	NM_001371.4		c.1311+829T>C		intron	N/A	NP_001362.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.1962+829T>C		intron	N/A	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.1311+829T>C		intron	N/A	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.1962+829T>C		intron	N/A	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14529 AN: 152050 Hom.: 1293 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0793

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0673

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0871

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0955 AC: 14533 AN: 152168 Hom.: 1292 Cov.: 32 AF XY: 0.0988 AC XY: 7352 AN XY: 74398

African (AFR) AF: 0.140 AC: 5807 AN: 41514

American (AMR) AF: 0.102 AC: 1556 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3466

East Asian (EAS) AF: 0.439 AC: 2258 AN: 5144

South Asian (SAS) AF: 0.175 AC: 844 AN: 4814

European-Finnish (FIN) AF: 0.0673 AC: 714 AN: 10608

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0444 AC: 3023 AN: 68010

Other (OTH) AF: 0.0881 AC: 186 AN: 2112

Alfa AF: 0.0724 Hom.: 351

Bravo AF: 0.101

Asia WGS AF: 0.270 AC: 940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.79
PhyloP100		0.47
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: rs1738262; hg19: chr6-38744556;