NM_144666.3:c.747-1179G>A

Variant names:

• chr11-6501574-G-A
• rs2555155
• NM_144666.3:c.747-1179G>A

Variant summary

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

The NM_144666.3(DNHD1):​c.747-1179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,626 control chromosomes in the GnomAD database, including 24,603 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 0.56 (24603 hom., cov: 29)
• Consequence: DNHD1 NM_144666.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 14 publications found

Genes affected

DNHD1 (HGNC:26532): (dynein heavy chain domain 1) Predicted to enable dynein intermediate chain binding activity; dynein light intermediate chain binding activity; and minus-end-directed microtubule motor activity. Predicted to be involved in cilium movement. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

DNHD1 Gene-Disease associations (from GenCC):

• spermatogenic failure 65

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000283977 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNHD1	NM_144666.3	c.747-1179G>A		intron_variant	Intron 3 of 42	ENST00000254579.11	NP_653267.2
DNHD1	NM_173589.4	c.747-1179G>A		intron_variant	Intron 2 of 7		NP_775860.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNHD1	ENST00000254579.11	c.747-1179G>A		intron_variant	Intron 3 of 42	5	NM_144666.3	ENSP00000254579.6
DNHD1	ENST00000354685.7	c.747-1179G>A		intron_variant	Intron 2 of 7	1		ENSP00000346716.3
DNHD1	ENST00000473019.5	n.395-1179G>A		intron_variant	Intron 3 of 3	2
ENSG00000283977	ENST00000639224.1	n.*69-1179G>A		intron_variant	Intron 2 of 3	4		ENSP00000492738.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84546 AN: 151508 Hom.: 24583 Cov.: 29

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.558 AC: 84617 AN: 151626 Hom.: 24603 Cov.: 29 AF XY: 0.548 AC XY: 40624 AN XY: 74068

African (AFR) AF: 0.696 AC: 28742 AN: 41306

American (AMR) AF: 0.527 AC: 8040 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1808 AN: 3460

East Asian (EAS) AF: 0.160 AC: 823 AN: 5142

South Asian (SAS) AF: 0.457 AC: 2189 AN: 4792

European-Finnish (FIN) AF: 0.428 AC: 4496 AN: 10496

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36780 AN: 67868

Other (OTH) AF: 0.536 AC: 1131 AN: 2110

Alfa AF: 0.534 Hom.: 14947

Bravo AF: 0.569

Asia WGS AF: 0.332 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.36
PhyloP100		-0.64
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: rs2555155; hg19: chr11-6522804;