Genetic Variant LRFN2:p.Gly634Arg (chr6-40392413-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020737.3(LRFN2):c.1900G>A(p.Gly634Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. G634W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LRFN2
NM_020737.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.34

Publications

0 publications found

Variant links:

Genes affected

LRFN2 (HGNC:21226): (leucine rich repeat and fibronectin type III domain containing 2) Predicted to be involved in modulation of chemical synaptic transmission and regulation of postsynapse organization. Predicted to be located in plasma membrane. Predicted to be active in Schaffer collateral - CA1 synapse and cell surface. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRFN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15546429).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020737.3. 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
	LRFN2	NM_020737.3	MANE Select	c.1900G>A	p.Gly634Arg	missense	Exon 3 of 3	NP_065788.1	Q9ULH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRFN2	ENST00000338305.7	TSL:1 MANE Select	c.1900G>A	p.Gly634Arg	missense	Exon 3 of 3	ENSP00000345985.6	Q9ULH4
	LRFN2	ENST00000700335.1		c.1900G>A	p.Gly634Arg	missense	Exon 4 of 4	ENSP00000514953.1	A0A8V8TQ63

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.06e-7

AC:

AN:

1416276

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700688

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32286

American (AMR)

AF:

0.00

AC:

AN:

38208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25326

East Asian (EAS)

AF:

0.00

AC:

AN:

36890

South Asian (SAS)

AF:

0.00

AC:

AN:

81440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

9.18e-7

AC:

AN:

1088942

Other (OTH)

AF:

0.00

AC:

AN:

58694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.059

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.68

M_CAP

Benign

0.044

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

1.3

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.39

REVEL

Benign

0.046

Sift

Uncertain

0.012

Sift4G

Benign

0.12

Polyphen

0.24

Vest4

0.092

MutPred

0.28

Gain of MoRF binding (P = 0.0053)

MVP

0.69

MPC

0.44

ClinPred

0.17

GERP RS

4.6

Varity_R

0.084

gMVP

0.078

Mutation Taster

=96/4

polymorphism

(source)

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