XM_017006129.2:c.-1812C>A

Variant names:

• chr3-52314348-C-A
• rs730050
• XM_017006129.2:c.-1812C>A

Variant summary

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

The XM_017006129.2(DNAH1):​c.-1812C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,094 control chromosomes in the GnomAD database, including 10,996 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 0.36 (10996 hom., cov: 32)
• Consequence: DNAH1 XM_017006129.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 14 publications found

Genes affected

DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

DNAH1 Gene-Disease associations (from GenCC):

• spermatogenic failure 18

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• ciliary dyskinesia, primary, 37

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	XM_017006129.2	c.-1812C>A		5_prime_UTR_variant	Exon 1 of 80		XP_016861618.1
DNAH1	XM_017006130.2	c.-1812C>A		5_prime_UTR_variant	Exon 1 of 79		XP_016861619.1
DNAH1	XM_017006131.2	c.-1812C>A		5_prime_UTR_variant	Exon 1 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54349 AN: 151976 Hom.: 10990 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.357 AC: 54368 AN: 152094 Hom.: 10996 Cov.: 32 AF XY: 0.369 AC XY: 27409 AN XY: 74328

African (AFR) AF: 0.185 AC: 7665 AN: 41506

American (AMR) AF: 0.451 AC: 6886 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3023 AN: 5170

South Asian (SAS) AF: 0.528 AC: 2548 AN: 4826

European-Finnish (FIN) AF: 0.483 AC: 5098 AN: 10562

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26620 AN: 67962

Other (OTH) AF: 0.371 AC: 783 AN: 2112

Alfa AF: 0.382 Hom.: 22823

Bravo AF: 0.347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.41
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs730050; hg19: chr3-52348364;