Genetic Variant LYSMD2:p.Val75Leu (chr15-51737400-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_153374.3(LYSMD2):c.223G>C(p.Val75Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V75I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

LYSMD2
NM_153374.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.01

Publications

0 publications found

Variant links:

Genes affected

LYSMD2 (HGNC:28571): (LysM domain containing 2)

LYSMD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32597327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYSMD2	NM_153374.3 link	c.223G>C	p.Val75Leu	missense_variant	Exon 1 of 3	ENST00000267838.7	NP_699205.1	Q8IV50-1
LYSMD2	NM_001143917.2 link	c.1-12279G>C		intron_variant	Intron 1 of 2		NP_001137389.1	Q8IV50-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LYSMD2	ENST00000267838.7 link	c.223G>C	p.Val75Leu	missense_variant	Exon 1 of 3	1	NM_153374.3	ENSP00000267838.3	Q8IV50-1
LYSMD2	ENST00000454181.6 link	c.1-12279G>C		intron_variant	Intron 1 of 2	1		ENSP00000410424.2	Q8IV50-2
LYSMD2	ENST00000560491.2 link	c.-1+440G>C		intron_variant	Intron 1 of 2	3		ENSP00000453933.1	Q8IV50-2
LYSMD2	ENST00000558126.1 link	c.83-12409G>C		intron_variant	Intron 1 of 2	5		ENSP00000452715.1	H0YK98

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.66e-7

AC:

AN:

1305566

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

643896

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26398

American (AMR)

AF:

0.00

AC:

AN:

24476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22734

East Asian (EAS)

AF:

0.00

AC:

AN:

27738

South Asian (SAS)

AF:

0.00

AC:

AN:

71284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4194

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1042398

Other (OTH)

AF:

0.00

AC:

AN:

53836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

AF:

0.00000659

AC:

AN:

151794

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41352

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67904

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.048

Eigen

Benign

0.067

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.5

PhyloP100

4.0

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.93

REVEL

Uncertain

0.30

Sift

Benign

0.54

Sift4G

Benign

0.49

Polyphen

0.12

Vest4

0.30

MutPred

0.64

Gain of sheet (P = 0.0011);

MVP

0.63

MPC

0.16

ClinPred

0.71

GERP RS

4.2

PromoterAI

-0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.65

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over