rs3912622

Variant names:

• chr11-103250744-A-C
• rs3912622
• NM_001080463.2:c.10064-2541A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-103250744-A-C
• chr11-103250744-A-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.10064-2541A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,790 control chromosomes in the GnomAD database, including 4,219 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 0.23 (4219 hom., cov: 32)
• Consequence: DYNC2H1 NM_001080463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.10064-2541A>C		intron_variant	Intron 66 of 89	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.10043-2541A>C		intron_variant	Intron 65 of 88	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.10064-2541A>C		intron_variant	Intron 66 of 89		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.10043-2541A>C		intron_variant	Intron 65 of 88	1	NM_001377.3	ENSP00000364887.2
DYNC2H1	ENST00000334267.11	c.2205+116325A>C		intron_variant	Intron 15 of 19	1		ENSP00000334021.7

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35115 AN: 151672 Hom.: 4208 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.232 AC: 35150 AN: 151790 Hom.: 4219 Cov.: 32 AF XY: 0.229 AC XY: 16993 AN XY: 74206

African (AFR) AF: 0.198 AC: 8197 AN: 41436

American (AMR) AF: 0.206 AC: 3139 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1139 AN: 3460

East Asian (EAS) AF: 0.254 AC: 1309 AN: 5160

South Asian (SAS) AF: 0.255 AC: 1228 AN: 4818

European-Finnish (FIN) AF: 0.188 AC: 1978 AN: 10506

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17377 AN: 67872

Other (OTH) AF: 0.250 AC: 528 AN: 2108

Alfa AF: 0.252 Hom.: 17683

Bravo AF: 0.229

Asia WGS AF: 0.256 AC: 890 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.86
DANN	Benign	0.44
PhyloP100		-0.035
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: rs3912622; hg19: chr11-103121473;