rs313425

Variant names:

• chr11-103339456-G-A
• rs313425
• NM_001080463.2:c.12060+15466G>A

Variant summary

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

The NM_001080463.2(DYNC2H1):​c.12060+15466G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,138 control chromosomes in the GnomAD database, including 9,700 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 0.33 (9700 hom., cov: 33)
• Consequence: DYNC2H1 NM_001080463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• 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), 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.12060+15466G>A		intron_variant	Intron 83 of 89	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.12039+15466G>A		intron_variant	Intron 82 of 88	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.12060+15466G>A		intron_variant	Intron 83 of 89		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.12039+15466G>A		intron_variant	Intron 82 of 88	1	NM_001377.3	ENSP00000364887.2
DYNC2H1	ENST00000334267.11	c.2206-96487G>A		intron_variant	Intron 15 of 19	1		ENSP00000334021.7
DYNC2H1	ENST00000528670.5	n.*85+15466G>A		intron_variant	Intron 10 of 16	5		ENSP00000433451.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49996 AN: 152018 Hom.: 9700 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.329 AC: 49994 AN: 152138 Hom.: 9700 Cov.: 33 AF XY: 0.326 AC XY: 24244 AN XY: 74350

African (AFR) AF: 0.113 AC: 4681 AN: 41558

American (AMR) AF: 0.353 AC: 5402 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1410 AN: 5144

South Asian (SAS) AF: 0.279 AC: 1344 AN: 4818

European-Finnish (FIN) AF: 0.480 AC: 5073 AN: 10564

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.434 AC: 29486 AN: 67966

Other (OTH) AF: 0.342 AC: 723 AN: 2112

Alfa AF: 0.383 Hom.: 5185

Bravo AF: 0.316

Asia WGS AF: 0.269 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.9
DANN	Benign	0.73
PhyloP100		0.33
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: rs313425; hg19: chr11-103210184;