rs201043335

Variant names:

• chr11-103154567-G-A
• NM_001080463.2:c.3419G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-103154567-G-A
• chr11-103154567-G-C
• chr11-103154567-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001377.3(DYNC2H1):​c.3419G>A​(p.Gly1140Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000276 in 1,450,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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: 0.0000028 (0 hom.)
• Consequence: DYNC2H1 NM_001377.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.31

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08684933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.3419G>A	p.Gly1140Glu	missense_variant	Exon 23 of 90	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.3419G>A	p.Gly1140Glu	missense_variant	Exon 23 of 89	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.3419G>A	p.Gly1140Glu	missense_variant	Exon 23 of 90		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.3419G>A	p.Gly1140Glu	missense_variant	Exon 23 of 89	1	NM_001377.3	ENSP00000364887.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1450524 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720444

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: 0.00000361

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	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.58
DEOGEN2	Benign	0.10	.;T;T;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	T;.;T;.;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.087	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.78	.;N;N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	.;N;.;.;N
REVEL	Benign	0.089
Sift	Benign	1.0	.;T;.;.;T
Sift4G	Benign	1.0	.;T;.;.;T
Polyphen		0.0	.;B;B;B;B
Vest4		0.34, 0.34
MutPred		0.39		.;Gain of disorder (P = 0.0504);Gain of disorder (P = 0.0504);Gain of disorder (P = 0.0504);Gain of disorder (P = 0.0504);
MVP		0.39
MPC		0.078
ClinPred		0.18	T
GERP RS		2.5
Varity_R		0.11
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-103025296;