rs117178504

Variant names:

• chr11-103283059-C-A
• rs117178504
• NM_001080463.2:c.10885C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-103283059-C-A
• chr11-103283059-C-T
• chr11-103283059-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001377.3(DYNC2H1):​c.10864C>A​(p.Arg3622Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,607,294 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (6 hom., cov: 32)
  • Exomes 𝑓: 0.011 (105 hom.)
• Consequence: DYNC2H1 NM_001377.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.170
• Publications: 3 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

ENSG00000285878 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP6: Variant 11-103283059-C-A is Benign according to our data. Variant chr11-103283059-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 220090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00764 (1161/152062) while in subpopulation AMR AF = 0.0131 (200/15254). AF 95% confidence interval is 0.0116. There are 6 homozygotes in GnomAd4. There are 519 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.10885C>A	p.Arg3629Arg	synonymous	Exon 74 of 90	NP_001073932.1	Q8NCM8-2
	DYNC2H1	NM_001377.3	MANE Select	c.10864C>A	p.Arg3622Arg	synonymous	Exon 73 of 89	NP_001368.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2H1	ENST00000650373.2	MANE Plus Clinical	c.10885C>A	p.Arg3629Arg	synonymous	Exon 74 of 90	ENSP00000497174.1	Q8NCM8-2
	DYNC2H1	ENST00000375735.7	TSL:1 MANE Select	c.10864C>A	p.Arg3622Arg	synonymous	Exon 73 of 89	ENSP00000364887.2	Q8NCM8-1
	DYNC2H1	ENST00000334267.11	TSL:1	c.2205+148640C>A		intron	N/A	ENSP00000334021.7	Q8NCM8-3

Frequencies

GnomAD3 genomes AF: 0.00764 AC: 1161 AN: 151942 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00699 AC: 1722 AN: 246432 AF XY: 0.00688

Gnomad AFR exome AF: 0.00254

Gnomad AMR exome AF: 0.00798

Gnomad ASJ exome AF: 0.00911

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00210

Gnomad NFE exome AF: 0.0107

Gnomad OTH exome AF: 0.00907

GnomAD4 exome AF: 0.0109 AC: 15878 AN: 1455232 Hom.: 105 Cov.: 30 AF XY: 0.0105 AC XY: 7577 AN XY: 723560

African (AFR) AF: 0.00156 AC: 52 AN: 33372

American (AMR) AF: 0.00934 AC: 414 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 263 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39524

South Asian (SAS) AF: 0.000459 AC: 39 AN: 84904

European-Finnish (FIN) AF: 0.00286 AC: 152 AN: 53144

Middle Eastern (MID) AF: 0.00365 AC: 21 AN: 5752

European-Non Finnish (NFE) AF: 0.0129 AC: 14288 AN: 1108168

Other (OTH) AF: 0.0108 AC: 649 AN: 60096

GnomAD4 genome AF: 0.00764 AC: 1161 AN: 152062 Hom.: 6 Cov.: 32 AF XY: 0.00698 AC XY: 519 AN XY: 74346

African (AFR) AF: 0.00284 AC: 118 AN: 41510

American (AMR) AF: 0.0131 AC: 200 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00866 AC: 30 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4812

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 760 AN: 67920

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.00987 Hom.: 14

Bravo AF: 0.00914

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Asphyxiating thoracic dystrophy 3 (1)
-	-	1	Jeune thoracic dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	6.0
DANN	Benign	0.75
PhyloP100		0.17
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs117178504; hg19: chr11-103153788;