rs180861816

Variant names:

• chr11-103125212-C-G
• NM_001080463.2:c.1774C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-103125212-C-G
• chr11-103125212-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001377.3(DYNC2H1):​c.1774C>G​(p.Leu592Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DYNC2H1 NM_001377.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68

Genes affected

DYNC2H1 (HGNC:2962): (dynein cytoplasmic 2 heavy chain 1) This gene encodes a large cytoplasmic dynein protein that is involved in retrograde transport in the cilium and has a role in intraflagellar transport, a process required for ciliary/flagellar assembly. Mutations in this gene cause a heterogeneous spectrum of conditions related to altered primary cilium function and often involve polydactyly, abnormal skeletogenesis, and polycystic kidneys. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.758

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.1774C>G	p.Leu592Val	missense_variant	Exon 12 of 90	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.1774C>G	p.Leu592Val	missense_variant	Exon 12 of 89	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.1774C>G	p.Leu592Val	missense_variant	Exon 12 of 90		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.1774C>G	p.Leu592Val	missense_variant	Exon 12 of 89	1	NM_001377.3	ENSP00000364887.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461204 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726864

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	.;T;.;T;.;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;.;D;D;.;D
M_CAP	Benign	0.080	D
MetaRNN	Pathogenic	0.76	D;D;D;D;D;D
MetaSVM	Uncertain	0.083	D
MutationAssessor	Uncertain	2.6	.;M;M;M;M;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.2	.;N;N;.;.;N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0050	.;D;D;.;.;D
Sift4G	Uncertain	0.012	.;D;D;.;.;D
Polyphen		1.0, 1.0, 1.0	.;D;D;D;D;D
Vest4		0.73, 0.81, 0.73
MutPred		0.77		Loss of stability (P = 0.064);Loss of stability (P = 0.064);Loss of stability (P = 0.064);Loss of stability (P = 0.064);Loss of stability (P = 0.064);Loss of stability (P = 0.064);
MVP		0.78
MPC		0.37
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.32
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-102995941;