rs116666272

Variant names:

• chr11-103116593-A-G
• rs116666272
• NM_001080463.2:c.645A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-103116593-A-G
• chr11-103116593-A-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001377.3(DYNC2H1):​c.645A>G​(p.Leu215Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,606,950 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (50 hom.)
• Consequence: DYNC2H1 NM_001377.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.68
• Publications: 1 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-103116593-A-G is Benign according to our data. Variant chr11-103116593-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 302004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

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.645A>G	p.Leu215Leu	synonymous	Exon 5 of 90	NP_001073932.1	Q8NCM8-2
	DYNC2H1	NM_001377.3	MANE Select	c.645A>G	p.Leu215Leu	synonymous	Exon 5 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.645A>G	p.Leu215Leu	synonymous	Exon 5 of 90	ENSP00000497174.1	Q8NCM8-2
	DYNC2H1	ENST00000375735.7	TSL:1 MANE Select	c.645A>G	p.Leu215Leu	synonymous	Exon 5 of 89	ENSP00000364887.2	Q8NCM8-1
	DYNC2H1	ENST00000334267.11	TSL:1	c.645A>G	p.Leu215Leu	synonymous	Exon 5 of 20	ENSP00000334021.7	Q8NCM8-3

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2356 AN: 152128 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00410 AC: 1009 AN: 245912 AF XY: 0.00308

Gnomad AFR exome AF: 0.0541

Gnomad AMR exome AF: 0.00347

Gnomad ASJ exome AF: 0.000700

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000402

Gnomad OTH exome AF: 0.00254

GnomAD4 exome AF: 0.00180 AC: 2618 AN: 1454704 Hom.: 50 Cov.: 30 AF XY: 0.00157 AC XY: 1138 AN XY: 723622

African (AFR) AF: 0.0563 AC: 1870 AN: 33228

American (AMR) AF: 0.00400 AC: 177 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.000694 AC: 18 AN: 25950

East Asian (EAS) AF: 0.00 AC: 0 AN: 39364

South Asian (SAS) AF: 0.000129 AC: 11 AN: 85022

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 53028

Middle Eastern (MID) AF: 0.00976 AC: 56 AN: 5736

European-Non Finnish (NFE) AF: 0.000195 AC: 216 AN: 1108120

Other (OTH) AF: 0.00448 AC: 269 AN: 60046

GnomAD4 genome AF: 0.0155 AC: 2357 AN: 152246 Hom.: 55 Cov.: 32 AF XY: 0.0153 AC XY: 1141 AN XY: 74440

African (AFR) AF: 0.0524 AC: 2178 AN: 41534

American (AMR) AF: 0.00804 AC: 123 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000324 AC: 22 AN: 67992

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00717 Hom.: 18

Bravo AF: 0.0177

Asia WGS AF: 0.00578 AC: 20 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Asphyxiating thoracic dystrophy 3 (2)
-	-	1	Jeune thoracic dystrophy (1)
-	-	1	not provided (1)
-	-	1	Short rib-polydactyly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.32
PhyloP100		-3.7
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs116666272; hg19: chr11-102987322;