rs562139820

Variant names:

• chr11-103257731-C-A
• NM_001080463.2:c.10606C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-103257731-C-A
• chr11-103257731-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001377.3(DYNC2H1):​c.10585C>A​(p.Arg3529Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DYNC2H1 NM_001377.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648

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]

ENSG00000285878 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP7: Synonymous conserved (PhyloP=0.648 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.10606C>A	p.Arg3536Arg	synonymous_variant	Exon 70 of 90	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.10585C>A	p.Arg3529Arg	synonymous_variant	Exon 69 of 89	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.10606C>A	p.Arg3536Arg	synonymous_variant	Exon 70 of 90		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.10585C>A	p.Arg3529Arg	synonymous_variant	Exon 69 of 89	1	NM_001377.3	ENSP00000364887.2
DYNC2H1	ENST00000334267.11	c.2205+123312C>A		intron_variant	Intron 15 of 19	1		ENSP00000334021.7
ENSG00000285878	ENST00000649070.1	n.691-5427G>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446742 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 718482

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000389

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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
BayesDel_noAF	Benign	-0.22
CADD	Benign	6.6
DANN	Benign	0.77

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: chr11-103128460;