rs778505007

Variant names:

• chr6-38722993-C-T
• rs778505007
• NM_001206927.2:c.184C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-38722993-C-T
• chr6-38722993-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371.4(DNAH8):​c.-383C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: DNAH8 NM_001371.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.862
• Publications: 3 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: ClinGen, Labcorp Genetics (formerly Invitae)
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11020848).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371.4. 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.184C>T	p.Arg62Trp	missense	Exon 2 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.-383C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 92	NP_001362.2	Q96JB1-1
	DNAH8	NM_001371.4		c.-383C>T		5_prime_UTR	Exon 2 of 92	NP_001362.2	Q96JB1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.184C>T	p.Arg62Trp	missense	Exon 2 of 93	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000373278.8	TSL:1	c.184C>T	p.Arg62Trp	missense	Exon 2 of 5	ENSP00000362375.4	Q8IU65
	DNAH8	ENST00000449981.6	TSL:5	c.184C>T	p.Arg62Trp	missense	Exon 1 of 82	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 243816 AF XY: 0.00

Gnomad AFR exome AF: 0.0000701

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74296

African (AFR) AF: 0.0000483 AC: 2 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000863 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.3
DANN	Uncertain	0.97
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.86
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.094
Sift	Uncertain	0.014	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.34		Loss of disorder (P = 0.0045)
MVP		0.10
ClinPred		0.99	D
GERP RS		-10
PromoterAI		-0.058	Neutral
gMVP		0.30
Mutation Taster		=99/1	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: rs778505007; hg19: chr6-38690769; COSMIC: COSV104403478; COSMIC: COSV104403478;