11-103468149-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080463.2(DYNC2H1):c.12670-440A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,166 control chromosomes in the GnomAD database, including 2,197 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 0.16 (2197 hom., cov: 33)
• Consequence: DYNC2H1 NM_001080463.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2H1	NM_001080463.2	c.12670-440A>G		intron_variant		ENST00000650373.2
DYNC2H1	NM_001377.3	c.12649-440A>G		intron_variant		ENST00000375735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2H1	ENST00000375735.7	c.12649-440A>G		intron_variant		1	NM_001377.3	P3
DYNC2H1	ENST00000650373.2	c.12670-440A>G		intron_variant			NM_001080463.2	A1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24857 AN: 152046 Hom.: 2186 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.164 AC: 24880 AN: 152166 Hom.: 2197 Cov.: 33 AF XY: 0.167 AC XY: 12450 AN XY: 74418

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.153

Alfa AF: 0.105 Hom.: 217

Bravo AF: 0.171

Asia WGS AF: 0.238 AC: 826 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.39
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs12418302; hg19: chr11-103338877;