11-103186317-CGA-AGG

Variant names:

• chr11-103186317-CGA-AGG
• NM_001080463.2:c.6709_6711delCGAinsAGG
• DYNC2H1 p.2238

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_001377.3(DYNC2H1):​c.6709_6711delCGAinsAGG​(p.2238) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R2237R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: DYNC2H1 NM_001377.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 0 publications found

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]

DYNC2H1 Gene-Disease associations (from GenCC):

• asphyxiating thoracic dystrophy 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P, ClinGen
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short rib-polydactyly syndrome, Majewski type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short rib-polydactyly syndrome, Verma-Naumoff type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=2.59 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2H1	NM_001080463.2	MANE Plus Clinical	c.6709_6711delCGAinsAGG	p.2238	synonymous	N/A	NP_001073932.1	Q8NCM8-2
	DYNC2H1	NM_001377.3	MANE Select	c.6709_6711delCGAinsAGG	p.2238	synonymous	N/A	NP_001368.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2H1	ENST00000650373.2	MANE Plus Clinical	c.6709_6711delCGAinsAGG	p.2238	synonymous	N/A	ENSP00000497174.1	Q8NCM8-2
	DYNC2H1	ENST00000375735.7	TSL:1 MANE Select	c.6709_6711delCGAinsAGG	p.2238	synonymous	N/A	ENSP00000364887.2	Q8NCM8-1
	DYNC2H1	ENST00000334267.11	TSL:1	c.2205+51898_2205+51900delCGAinsAGG		intron	N/A	ENSP00000334021.7	Q8NCM8-3

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-103057046;