rs2267420

Variant names:

• chr22-39952516-G-A
• rs2267420
• NM_004810.4:c.79-3303G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004810.4(GRAP2):​c.79-3303G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,100 control chromosomes in the GnomAD database, including 1,534 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1534 hom., cov: 31)
• Consequence: GRAP2 NM_004810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 4 publications found

Genes affected

GRAP2 (HGNC:4563): (GRB2 related adaptor protein 2) This gene encodes a member of the GRB2/Sem5/Drk family. This member is an adaptor-like protein involved in leukocyte-specific protein-tyrosine kinase signaling. Like its related family member, GRB2-related adaptor protein (GRAP), this protein contains an SH2 domain flanked by two SH3 domains. This protein interacts with other proteins, such as GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAP2	NM_004810.4	c.79-3303G>A		intron_variant	Intron 2 of 7	ENST00000344138.9	NP_004801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAP2	ENST00000344138.9	c.79-3303G>A		intron_variant	Intron 2 of 7	1	NM_004810.4	ENSP00000339186.4
GRAP2	ENST00000407075.3	c.79-3303G>A		intron_variant	Intron 1 of 6	1		ENSP00000385607.3
GRAP2	ENST00000420971.5	c.79-3303G>A		intron_variant	Intron 2 of 3	2		ENSP00000396355.1
GRAP2	ENST00000478445.1	n.252-3303G>A		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19217 AN: 151982 Hom.: 1536 Cov.: 31

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.148

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.126 AC: 19216 AN: 152100 Hom.: 1534 Cov.: 31 AF XY: 0.128 AC XY: 9513 AN XY: 74352

African (AFR) AF: 0.0322 AC: 1336 AN: 41500

American (AMR) AF: 0.126 AC: 1924 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3468

East Asian (EAS) AF: 0.147 AC: 757 AN: 5166

South Asian (SAS) AF: 0.114 AC: 549 AN: 4816

European-Finnish (FIN) AF: 0.195 AC: 2060 AN: 10574

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11203 AN: 67986

Other (OTH) AF: 0.147 AC: 310 AN: 2108

Alfa AF: 0.154 Hom.: 1464

Bravo AF: 0.116

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.91
DANN	Benign	0.77
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2267420; hg19: chr22-40348520;