3-196296136-C-T

Variant names:

• chr3-196296136-C-T
• rs73212151
• NM_152773.5:c.318-67G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152773.5(DYNLT2B):​c.318-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 1,323,530 control chromosomes in the GnomAD database, including 3,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (380 hom., cov: 32)
  • Exomes 𝑓: 0.065 (2989 hom.)
• Consequence: DYNLT2B NM_152773.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.37

Genes affected

DYNLT2B (HGNC:28482): (dynein light chain Tctex-type 2B) 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 subunit of the human cytoplasmic dynein-2 complex. Mutations in this gene are associated with short-rib thoracic dysplasia 17 with or without polydactyly. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

ENSG00000272741 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-196296136-C-T is Benign according to our data. Variant chr3-196296136-C-T is described in ClinVar as [Benign]. Clinvar id is 1262426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNLT2B	NM_152773.5	c.318-67G>A		intron_variant	Intron 3 of 4	ENST00000325318.10	NP_689986.2
DYNLT2B	NM_001351628.2	c.318-67G>A		intron_variant	Intron 3 of 4		NP_001338557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNLT2B	ENST00000325318.10	c.318-67G>A		intron_variant	Intron 3 of 4	1	NM_152773.5	ENSP00000324323.5
ENSG00000272741	ENST00000431391.1	n.317+10807G>A		intron_variant	Intron 3 of 5	5		ENSP00000405181.1

Frequencies

GnomAD3 genomes AF: 0.0654 AC: 9956 AN: 152134 Hom.: 379 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0447

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0611

GnomAD4 exome AF: 0.0653 AC: 76540 AN: 1171278 Hom.: 2989 Cov.: 16 AF XY: 0.0682 AC XY: 40655 AN XY: 596286

Gnomad4 AFR exome AF: 0.0746 AC: 2057 AN: 27578

Gnomad4 AMR exome AF: 0.0336 AC: 1471 AN: 43756

Gnomad4 ASJ exome AF: 0.112 AC: 2709 AN: 24184

Gnomad4 EAS exome AF: 0.0170 AC: 650 AN: 38248

Gnomad4 SAS exome AF: 0.121 AC: 9657 AN: 79844

Gnomad4 FIN exome AF: 0.0404 AC: 2142 AN: 53052

Gnomad4 NFE exome AF: 0.0630 AC: 53495 AN: 848668

Gnomad4 Remaining exome AF: 0.0732 AC: 3714 AN: 50754

GnomAD4 genome AF: 0.0654 AC: 9960 AN: 152252 Hom.: 380 Cov.: 32 AF XY: 0.0659 AC XY: 4902 AN XY: 74434

Gnomad4 AFR AF: 0.0760 AC: 0.0759603 AN: 0.0759603

Gnomad4 AMR AF: 0.0446 AC: 0.044581 AN: 0.044581

Gnomad4 ASJ AF: 0.112 AC: 0.111527 AN: 0.111527

Gnomad4 EAS AF: 0.0167 AC: 0.0167436 AN: 0.0167436

Gnomad4 SAS AF: 0.123 AC: 0.123288 AN: 0.123288

Gnomad4 FIN AF: 0.0372 AC: 0.0371909 AN: 0.0371909

Gnomad4 NFE AF: 0.0648 AC: 0.0647827 AN: 0.0647827

Gnomad4 OTH AF: 0.0605 AC: 0.0604915 AN: 0.0604915

Alfa AF: 0.0680 Hom.: 99

Bravo AF: 0.0652

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.024
DANN	Benign	0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73212151; hg19: chr3-196023007;