14-52007912-A-T

Variant names:

• chr14-52007912-A-T
• rs1020876205
• NM_007361.4:c.3778T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007361.4(NID2):​c.3778T>A​(p.Leu1260Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L1260V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NID2 NM_007361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3778T>A	p.Leu1260Ile	missense	Exon 19 of 22	NP_031387.3
	RTRAF	NM_016039.3	MANE Select	c.*3396A>T		3_prime_UTR	Exon 8 of 8	NP_057123.1	Q9Y224

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NID2	ENST00000216286.10	TSL:1 MANE Select	c.3778T>A	p.Leu1260Ile	missense	Exon 19 of 22	ENSP00000216286.4	Q14112-1
	RTRAF	ENST00000261700.8	TSL:1 MANE Select	c.*3396A>T		3_prime_UTR	Exon 8 of 8	ENSP00000261700.3	Q9Y224
	NID2	ENST00000556572.1	TSL:2	c.1582T>A	p.Leu528Ile	missense	Exon 10 of 13	ENSP00000452190.1	H0YJV3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000287 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.029
Eigen_PC	Benign	0.093
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.0
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.28
Sift	Benign	0.089	T
Sift4G	Benign	0.17	T
Polyphen		0.61	P
Vest4		0.23
MutPred		0.72		Gain of catalytic residue at E1263 (P = 0.0425)
MVP		0.75
MPC		0.21
ClinPred		0.26	T
GERP RS		2.0
Varity_R		0.059
gMVP		0.63
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.37		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1020876205; hg19: chr14-52474630;