rs1738240

Variant names:

• chr6-38795957-C-T
• rs1738240
• NM_001206927.2:c.2901+4283C>T

Variant summary

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

The NM_001206927.2(DNAH8):​c.2901+4283C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,022 control chromosomes in the GnomAD database, including 32,181 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 0.65 (32181 hom., cov: 31)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812
• Publications: 2 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.2901+4283C>T		intron_variant	Intron 21 of 92	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.2901+4283C>T		intron_variant	Intron 21 of 92	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.2250+4283C>T		intron_variant	Intron 19 of 90	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.2901+4283C>T		intron_variant	Intron 20 of 81	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98212 AN: 151904 Hom.: 32118 Cov.: 31

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.647 AC: 98335 AN: 152022 Hom.: 32181 Cov.: 31 AF XY: 0.646 AC XY: 47961 AN XY: 74284

African (AFR) AF: 0.644 AC: 26703 AN: 41456

American (AMR) AF: 0.700 AC: 10689 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1987 AN: 3472

East Asian (EAS) AF: 0.847 AC: 4378 AN: 5170

South Asian (SAS) AF: 0.682 AC: 3280 AN: 4810

European-Finnish (FIN) AF: 0.582 AC: 6136 AN: 10544

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43074 AN: 67972

Other (OTH) AF: 0.623 AC: 1316 AN: 2112

Alfa AF: 0.640 Hom.: 119907

Bravo AF: 0.657

Asia WGS AF: 0.766 AC: 2666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.84
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs1738240; hg19: chr6-38763733;