rs11225703

Variant names:

• chr11-103315230-C-T
• rs11225703
• NM_001080463.2:c.11671-1315C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080463.2(DYNC2H1):​c.11671-1315C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,830 control chromosomes in the GnomAD database, including 7,271 homozygotes. 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: 𝑓 0.30 (7271 hom., cov: 32)
• Consequence: DYNC2H1 NM_001080463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 6 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), G2P, Orphanet, Ambry Genetics
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.11671-1315C>T		intron_variant	Intron 80 of 89	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.11650-1315C>T		intron_variant	Intron 79 of 88	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.11671-1315C>T		intron_variant	Intron 80 of 89		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.11650-1315C>T		intron_variant	Intron 79 of 88	1	NM_001377.3	ENSP00000364887.2
DYNC2H1	ENST00000334267.11	c.2206-120713C>T		intron_variant	Intron 15 of 19	1		ENSP00000334021.7
DYNC2H1	ENST00000528670.5	n.829-1315C>T		intron_variant	Intron 7 of 16	5		ENSP00000433451.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46028 AN: 151712 Hom.: 7272 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.303 AC: 46033 AN: 151830 Hom.: 7271 Cov.: 32 AF XY: 0.301 AC XY: 22360 AN XY: 74190

African (AFR) AF: 0.209 AC: 8676 AN: 41464

American (AMR) AF: 0.310 AC: 4726 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1428 AN: 5174

South Asian (SAS) AF: 0.249 AC: 1202 AN: 4830

European-Finnish (FIN) AF: 0.415 AC: 4366 AN: 10528

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23313 AN: 67820

Other (OTH) AF: 0.305 AC: 642 AN: 2106

Alfa AF: 0.336 Hom.: 32124

Bravo AF: 0.298

Asia WGS AF: 0.265 AC: 921 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		-1.3
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: rs11225703; hg19: chr11-103185959;