Genetic Variant NM_007361.4:c.3914G>A (chr14-52006627-C-T) – 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_007361.4(NID2):c.3914G>A(p.Gly1305Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G1305A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NID2
NM_007361.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.00

Publications

0 publications found

Variant links:

Genes affected

NID2 (HGNC:13389): (nidogen 2) This gene encodes a member of the nidogen family of basement membrane proteins. This protein is a cell-adhesion protein that binds collagens I and IV and laminin and may be involved in maintaining the structure of the basement membrane.[provided by RefSeq, Jun 2010]

NID2 links:

RTRAF (HGNC:23169): (RNA transcription, translation and transport factor) Enables RNA binding activity; RNA polymerase II complex binding activity; and identical protein binding activity. Involved in negative regulation of protein kinase activity; positive regulation of transcription by RNA polymerase II; and tRNA splicing, via endonucleolytic cleavage and ligation. Located in microtubule cytoskeleton; nucleoplasm; and perinuclear region of cytoplasm. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

RTRAF 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, 0.843

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007361.4. 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
	NID2	NM_007361.4	MANE Select	c.3914G>A	p.Gly1305Glu	missense	Exon 20 of 22	NP_031387.3
	RTRAF	NM_016039.3	MANE Select	c.*2111C>T		3_prime_UTR	Exon 8 of 8	NP_057123.1	Q9Y224

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NID2	ENST00000216286.10	TSL:1 MANE Select	c.3914G>A	p.Gly1305Glu	missense	Exon 20 of 22	ENSP00000216286.4	Q14112-1
RTRAF	ENST00000261700.8	TSL:1 MANE Select	c.*2111C>T		3_prime_UTR	Exon 8 of 8	ENSP00000261700.3	Q9Y224
NID2	ENST00000556572.1	TSL:2	c.1718G>A	p.Gly573Glu	missense	Exon 11 of 13	ENSP00000452190.1	H0YJV3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251402

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.84

MetaSVM

Uncertain

0.42

MutationAssessor

Pathogenic

4.0

PhyloP100

5.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.45

Sift

Uncertain

0.014

Sift4G

Benign

0.27

Polyphen

0.99

Vest4

0.87

MutPred

0.65

Gain of catalytic residue at R1309 (P = 0.024)

MVP

0.65

MPC

0.53

ClinPred

0.99

GERP RS

6.0

Varity_R

0.74

gMVP

0.92

Mutation Taster

=17/83

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over