rs7926700

Variant names:

• chr11-103324076-C-G
• rs7926700
• NM_001080463.2:c.12060+86C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-103324076-C-G
• chr11-103324076-C-A
• chr11-103324076-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001377.3(DYNC2H1):​c.12039+86C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 697,124 control chromosomes in the GnomAD database, including 933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (639 hom., cov: 32)
  • Exomes 𝑓: 0.020 (294 hom.)
• Consequence: DYNC2H1 NM_001377.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.85
• 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-103324076-C-G is Benign according to our data. Variant chr11-103324076-C-G is described in ClinVar as Benign. ClinVar VariationId is 675083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 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.12060+86C>G		intron	N/A	NP_001073932.1	Q8NCM8-2
	DYNC2H1	NM_001377.3	MANE Select	c.12039+86C>G		intron	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.12060+86C>G		intron	N/A	ENSP00000497174.1	Q8NCM8-2
	DYNC2H1	ENST00000375735.7	TSL:1 MANE Select	c.12039+86C>G		intron	N/A	ENSP00000364887.2	Q8NCM8-1
	DYNC2H1	ENST00000334267.11	TSL:1	c.2206-111867C>G		intron	N/A	ENSP00000334021.7	Q8NCM8-3

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8860 AN: 152070 Hom.: 638 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0490

GnomAD4 exome AF: 0.0201 AC: 10938 AN: 544936 Hom.: 294 AF XY: 0.0199 AC XY: 5477 AN XY: 274596

African (AFR) AF: 0.167 AC: 2121 AN: 12728

American (AMR) AF: 0.0259 AC: 308 AN: 11888

Ashkenazi Jewish (ASJ) AF: 0.0555 AC: 703 AN: 12664

East Asian (EAS) AF: 0.0000383 AC: 1 AN: 26100

South Asian (SAS) AF: 0.00524 AC: 86 AN: 16404

European-Finnish (FIN) AF: 0.00655 AC: 201 AN: 30676

Middle Eastern (MID) AF: 0.0475 AC: 167 AN: 3518

European-Non Finnish (NFE) AF: 0.0161 AC: 6527 AN: 404804

Other (OTH) AF: 0.0315 AC: 824 AN: 26154

GnomAD4 genome AF: 0.0583 AC: 8876 AN: 152188 Hom.: 639 Cov.: 32 AF XY: 0.0567 AC XY: 4223 AN XY: 74424

African (AFR) AF: 0.163 AC: 6759 AN: 41504

American (AMR) AF: 0.0331 AC: 507 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 202 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4822

European-Finnish (FIN) AF: 0.00415 AC: 44 AN: 10598

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0180 AC: 1221 AN: 68010

Other (OTH) AF: 0.0475 AC: 100 AN: 2104

Alfa AF: 0.00941 Hom.: 9

Bravo AF: 0.0650

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.38
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs7926700; hg19: chr11-103194804;