dbSNP rs11866734: DYNLRB2:p.Leu66Met (chr16-80549600-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_130897.3(DYNLRB2):c.196C>A(p.Leu66Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L66L) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DYNLRB2
NM_130897.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.73

Publications

10 publications found

Variant links:

Genes affected

DYNLRB2 (HGNC:15467): (dynein light chain roadblock-type 2) Predicted to enable dynein intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be located in ciliary tip. Predicted to be part of cytoplasmic dynein complex. Predicted to be active in centrosome and cytoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

DYNLRB2 links:

DYNLRB2-AS1 (HGNC:55405): (DYNLRB2 antisense RNA 1)

DYNLRB2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.925

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130897.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DYNLRB2	NM_130897.3	MANE Select	c.196C>A	p.Leu66Met	missense	Exon 3 of 4	NP_570967.1
DYNLRB2	NM_001305017.2		c.283C>A	p.Leu95Met	missense	Exon 3 of 4	NP_001291946.1
DYNLRB2	NR_130942.2		n.821C>A		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DYNLRB2	ENST00000305904.11	TSL:1 MANE Select	c.196C>A	p.Leu66Met	missense	Exon 3 of 4	ENSP00000302936.6
DYNLRB2	ENST00000338542.9	TSL:1	n.*121C>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000342009.5
DYNLRB2	ENST00000338542.9	TSL:1	n.*121C>A		3_prime_UTR	Exon 4 of 5	ENSP00000342009.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

250944

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726218

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

86048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110622

Other (OTH)

AF:

0.00

AC:

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

M_CAP

Benign

0.047

MetaRNN

Pathogenic

0.93

MetaSVM

Benign

-0.63

PhyloP100

2.7

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.9

REVEL

Benign

0.24

Sift

Uncertain

0.025

Sift4G

Uncertain

0.037

Polyphen

0.99

Vest4

0.45

MutPred

0.87

Gain of disorder (P = 0.1138)

MVP

0.32

MPC

0.017

ClinPred

0.92

GERP RS

4.1

Varity_R

0.25

gMVP

0.63

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over