11-103170468-T-C

Variant names:

• chr11-103170468-T-C
• rs634192
• NM_001080463.2:c.5151+178T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001377.3(DYNC2H1):​c.5151+178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,062 control chromosomes in the GnomAD database, including 35,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (35549 hom., cov: 32)
• Consequence: DYNC2H1 NM_001377.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.237

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-103170468-T-C is Benign according to our data. Variant chr11-103170468-T-C is described in ClinVar as [Benign]. Clinvar id is 667695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.5151+178T>C		intron_variant	Intron 33 of 89	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.5151+178T>C		intron_variant	Intron 33 of 88	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.5151+178T>C		intron_variant	Intron 33 of 89		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.5151+178T>C		intron_variant	Intron 33 of 88	1	NM_001377.3	ENSP00000364887.2
DYNC2H1	ENST00000334267.11	c.2205+36049T>C		intron_variant	Intron 15 of 19	1		ENSP00000334021.7
DYNC2H1	ENST00000649323.1	n.*2696+178T>C		intron_variant	Intron 31 of 50			ENSP00000497581.1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102602 AN: 151944 Hom.: 35523 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.675 AC: 102669 AN: 152062 Hom.: 35549 Cov.: 32 AF XY: 0.678 AC XY: 50436 AN XY: 74338

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.681

Alfa AF: 0.700 Hom.: 4744

Bravo AF: 0.668

Asia WGS AF: 0.706 AC: 2442 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.83

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: rs634192; hg19: chr11-103041197;