chr2-164497017-A-C

Variant names:

• chr2-164497017-A-C
• NM_004490.3:c.1373T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004490.3(GRB14):​c.1373T>G​(p.Leu458Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRB14 NM_004490.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

Genes affected

GRB14 (HGNC:4565): (growth factor receptor bound protein 14) The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors. This protein likely has an inhibitory effect on receptor tyrosine kinase signaling and, in particular, on insulin receptor signaling. This gene may play a role in signaling pathways that regulate growth and metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB14	NM_004490.3	c.1373T>G	p.Leu458Arg	missense_variant	Exon 12 of 14	ENST00000263915.8	NP_004481.2
GRB14	NM_001303422.2	c.1112T>G	p.Leu371Arg	missense_variant	Exon 11 of 13		NP_001290351.1
GRB14	XM_047444013.1	c.773T>G	p.Leu258Arg	missense_variant	Exon 11 of 13		XP_047299969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB14	ENST00000263915.8	c.1373T>G	p.Leu458Arg	missense_variant	Exon 12 of 14	1	NM_004490.3	ENSP00000263915.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.92	D;T
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Benign	0.86	L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.60
Sift	Benign	0.049	D;D
Sift4G	Benign	0.11	T;.
Polyphen		0.038	B;.
Vest4		0.72
MutPred		0.53		Gain of MoRF binding (P = 0.0268);.;
MVP		0.92
MPC		0.094
ClinPred		0.90	D
GERP RS		1.7
Varity_R		0.79
gMVP		0.46

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: chr2-165353527;