chr3-196316347-A-AT

Variant names:

• chr3-196316347-A-AT
• rs61388787
• NM_152773.5:c.114-117dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_152773.5(DYNLT2B):​c.114-117dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,046,880 control chromosomes in the GnomAD database, including 2,258 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (373 hom., cov: 31)
  • Exomes 𝑓: 0.058 (1885 hom.)
• Consequence: DYNLT2B NM_152773.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.446
• Publications: 0 publications found

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:):

TM4SF19-DYNLT2B (HGNC:49190): (TM4SF19-DYNLT2B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring transmembrane 4 L six family member 19 (TM4SF19) and Tctex1 domain containing 2 (TCTEX1D2) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus not expected to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-196316347-A-AT is Benign according to our data. Variant chr3-196316347-A-AT is described in ClinVar as Benign. ClinVar VariationId is 1232152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152773.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT2B	NM_152773.5	MANE Select	c.114-117dupA		intron	N/A	NP_689986.2	Q8WW35
	DYNLT2B	NM_001351628.2		c.114-117dupA		intron	N/A	NP_001338557.1
	TM4SF19-DYNLT2B	NR_037950.1		n.862-117dupA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT2B	ENST00000325318.10	TSL:1 MANE Select	c.114-117_114-116insA		intron	N/A	ENSP00000324323.5	Q8WW35
	ENSG00000272741	ENST00000431391.1	TSL:5	n.114-117_114-116insA		intron	N/A	ENSP00000405181.1	E7ESA3
	TM4SF19-DYNLT2B	ENST00000442633.1	TSL:1	n.*74-117_*74-116insA		intron	N/A	ENSP00000405973.1

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9910 AN: 151910 Hom.: 372 Cov.: 31

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0444

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0366

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0583 AC: 52152 AN: 894852 Hom.: 1885 AF XY: 0.0599 AC XY: 26369 AN XY: 440454

African (AFR) AF: 0.0683 AC: 1364 AN: 19968

American (AMR) AF: 0.0344 AC: 478 AN: 13896

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 1646 AN: 15520

East Asian (EAS) AF: 0.0155 AC: 466 AN: 29986

South Asian (SAS) AF: 0.110 AC: 4095 AN: 37384

European-Finnish (FIN) AF: 0.0363 AC: 1111 AN: 30610

Middle Eastern (MID) AF: 0.116 AC: 491 AN: 4216

European-Non Finnish (NFE) AF: 0.0566 AC: 39847 AN: 703862

Other (OTH) AF: 0.0673 AC: 2654 AN: 39410

GnomAD4 genome AF: 0.0652 AC: 9914 AN: 152028 Hom.: 373 Cov.: 31 AF XY: 0.0656 AC XY: 4878 AN XY: 74316

African (AFR) AF: 0.0758 AC: 3142 AN: 41466

American (AMR) AF: 0.0443 AC: 675 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3468

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5184

South Asian (SAS) AF: 0.123 AC: 593 AN: 4812

European-Finnish (FIN) AF: 0.0366 AC: 386 AN: 10554

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0646 AC: 4393 AN: 67980

Other (OTH) AF: 0.0606 AC: 128 AN: 2112

Alfa AF: 0.0163 Hom.: 11

Bravo AF: 0.0651

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61388787; hg19: chr3-196043218;