6-40392413-C-T

Variant names:

• chr6-40392413-C-T
• NM_020737.3:c.1900G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 15/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15546429).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRFN2	NM_020737.3	c.1900G>A	p.Gly634Arg	missense_variant	Exon 3 of 3	ENST00000338305.7	NP_065788.1
LRFN2	XM_011514762.3	c.1900G>A	p.Gly634Arg	missense_variant	Exon 3 of 3		XP_011513064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRFN2	ENST00000338305.7	c.1900G>A	p.Gly634Arg	missense_variant	Exon 3 of 3	1	NM_020737.3	ENSP00000345985.6
LRFN2	ENST00000700335.1	c.1900G>A	p.Gly634Arg	missense_variant	Exon 4 of 4			ENSP00000514953.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416276 Hom.: 0 Cov.: 34 AF XY: 0.00000143 AC XY: 1 AN XY: 700688

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.18e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.046
Sift	Uncertain	0.012	D
Sift4G	Benign	0.12	T
Polyphen		0.24	B
Vest4		0.092
MutPred		0.28		Gain of MoRF binding (P = 0.0053);
MVP		0.69
MPC		0.44
ClinPred		0.17	T
GERP RS		4.6
Varity_R		0.084
gMVP		0.078

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-40360152;