rs1043384862

Variant names:

• chr11-103165911-C-A
• NM_001080463.2:c.4625C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-103165911-C-A
• chr11-103165911-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001377.3(DYNC2H1):​c.4625C>A​(p.Ala1542Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000745 in 1,341,388 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: DYNC2H1 NM_001377.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.62

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.4625C>A	p.Ala1542Glu	missense_variant	Exon 31 of 90	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.4625C>A	p.Ala1542Glu	missense_variant	Exon 31 of 89	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.4625C>A	p.Ala1542Glu	missense_variant	Exon 31 of 90		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.4625C>A	p.Ala1542Glu	missense_variant	Exon 31 of 89	1	NM_001377.3	ENSP00000364887.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.45e-7 AC: 1 AN: 1341388 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 658794

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: 9.49e-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	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.75	D;D;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D;.;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Pathogenic	3.1	M;M;M;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.1	D;.;.;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0070	D;.;.;D
Sift4G	Uncertain	0.047	D;.;.;D
Polyphen		0.96	D;D;D;D
Vest4		0.87
MutPred		0.47		Gain of methylation at K1546 (P = 0.1147);Gain of methylation at K1546 (P = 0.1147);Gain of methylation at K1546 (P = 0.1147);Gain of methylation at K1546 (P = 0.1147);
MVP		0.69
MPC		0.34
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.57
gMVP		0.84

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: chr11-103036640;