chr14-101988596-C-A

Position:

• chr14-101988596-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000360184.10(DYNC1H1):​c.2719-107C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,447,390 control chromosomes in the GnomAD database, including 48,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (13150 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34881 hom.)
• Consequence: DYNC1H1 ENST00000360184.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.514

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-101988596-C-A is Benign according to our data. Variant chr14-101988596-C-A is described in ClinVar as [Benign]. Clinvar id is 674054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC1H1	NM_001376.5	c.2719-107C>A		intron_variant		ENST00000360184.10	NP_001367.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC1H1	ENST00000360184.10	c.2719-107C>A		intron_variant		1	NM_001376.5	ENSP00000348965	P1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53341 AN: 151988 Hom.: 13106 Cov.: 32

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.215 AC: 277904 AN: 1295282 Hom.: 34881 AF XY: 0.214 AC XY: 139140 AN XY: 651042

Gnomad4 AFR exome AF: 0.726

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.351 AC: 53446 AN: 152108 Hom.: 13150 Cov.: 32 AF XY: 0.346 AC XY: 25729 AN XY: 74362

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.343

Alfa AF: 0.208 Hom.: 6226

Bravo AF: 0.372

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.89
CADD	Benign	0.16
DANN	Benign	0.22

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: rs4906172; hg19: chr14-102454933;