rs1738262

Positions:

• chr6-38776780-T-C
• chr6-38776780-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206927.2(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 NM_001206927.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.1962+829T>C		intron_variant		ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.1962+829T>C		intron_variant		5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.1311+829T>C		intron_variant		2		A2
DNAH8	ENST00000449981.6	c.1962+829T>C		intron_variant		5

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

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.0673

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.0881

Alfa AF: 0.0365 Hom.: 40

Bravo AF: 0.101

Asia WGS AF: 0.270 AC: 940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs1738262; hg19: chr6-38744556;