2-164502282-G-A

Position:

• chr2-164502282-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_004490.3(GRB14):​c.1077C>T​(p.Gly359=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00795 in 1,605,388 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (70 hom.)
• Consequence: GRB14 NM_004490.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.13

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 Benign. Variant got -12 ACMG points.

• BP6: Variant 2-164502282-G-A is Benign according to our data. Variant chr2-164502282-G-A is described in ClinVar as [Benign]. Clinvar id is 779408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB14	NM_004490.3	c.1077C>T	p.Gly359=	synonymous_variant	9/14	ENST00000263915.8	NP_004481.2
GRB14	NM_001303422.2	c.816C>T	p.Gly272=	synonymous_variant	8/13		NP_001290351.1
GRB14	XM_047444013.1	c.477C>T	p.Gly159=	synonymous_variant	8/13		XP_047299969.1
GRB14	XR_427085.4	n.1303C>T		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB14	ENST00000263915.8	c.1077C>T	p.Gly359=	synonymous_variant	9/14	1	NM_004490.3	ENSP00000263915
GRB14	ENST00000446413.6	c.942C>T	p.Gly314=	synonymous_variant	9/12	1		ENSP00000416786
GRB14	ENST00000696453.2	c.816C>T	p.Gly272=	synonymous_variant	8/13			ENSP00000512640	P1
GRB14	ENST00000488342.5	n.1213C>T		non_coding_transcript_exon_variant	9/14	5

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 773 AN: 152002 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00520

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00870

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00481 AC: 1207 AN: 250774 Hom.: 7 AF XY: 0.00537 AC XY: 728 AN XY: 135516

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00317

Gnomad FIN exome AF: 0.00356

Gnomad NFE exome AF: 0.00795

Gnomad OTH exome AF: 0.00557

GnomAD4 exome AF: 0.00825 AC: 11989 AN: 1453268 Hom.: 70 Cov.: 27 AF XY: 0.00820 AC XY: 5931 AN XY: 723456

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00211

Gnomad4 ASJ exome AF: 0.00154

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00334

Gnomad4 FIN exome AF: 0.00341

Gnomad4 NFE exome AF: 0.00994

Gnomad4 OTH exome AF: 0.00588

GnomAD4 genome AF: 0.00508 AC: 773 AN: 152120 Hom.: 4 Cov.: 32 AF XY: 0.00473 AC XY: 352 AN XY: 74356

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00282

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00520

Gnomad4 NFE AF: 0.00870

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00633 Hom.: 3

Bravo AF: 0.00493

Asia WGS AF: 0.00145 AC: 5 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.1
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.22		Position offset: -27

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

Publications

LitVar

Other links and lift over

dbSNP: rs61748244; hg19: chr2-165358792;