rs2253998

chr14-102030015-C-A

Variant summary

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

The NM_001376.5(DYNC1H1):c.9762+77C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,610,468 control chromosomes in the GnomAD database, including 49,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (11694 hom., cov: 31)
  • Exomes 𝑓: 0.21 (37312 hom.)
• Consequence: DYNC1H1 NM_001376.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.04

Genes affected

DYNC1H1 (HGNC:2961): (dynein cytoplasmic 1 heavy chain 1) Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains.This gene encodes a member of the cytoplasmic dynein heavy chain family. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 14-102030015-C-A is Benign according to our data. Variant chr14-102030015-C-A is described in ClinVar as [Benign]. Clinvar id is 674055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC1H1	NM_001376.5	c.9762+77C>A		intron_variant		ENST00000360184.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC1H1	ENST00000360184.10	c.9762+77C>A		intron_variant		1	NM_001376.5	P1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50922 AN: 151568 Hom.: 11658 Cov.: 31

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.0960

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.211 AC: 307760 AN: 1458782 Hom.: 37312 Cov.: 33 AF XY: 0.211 AC XY: 152760 AN XY: 725654

Gnomad4 AFR exome AF: 0.686

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.336 AC: 51019 AN: 151686 Hom.: 11694 Cov.: 31 AF XY: 0.331 AC XY: 24542 AN XY: 74108

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.330

Alfa AF: 0.233 Hom.: 2728

Bravo AF: 0.356

Asia WGS AF: 0.283 AC: 983 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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	-0.88
Cadd	Benign	1.2
Dann	Benign	0.34

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: rs2253998; hg19: chr14-102496352; COSMIC: COSV64135223; COSMIC: COSV64135223;