rs201387983

Variant names:

• chr8-19364152-G-A
• rs201387983
• NM_022071.4:c.787G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-19364152-G-A
• chr8-19364152-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022071.4(SH2D4A):​c.787G>A​(p.Gly263Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000185 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SH2D4A NM_022071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58
• Publications: 2 publications found

Genes affected

SH2D4A (HGNC:26102): (SH2 domain containing 4A) Enables phosphatase binding activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10957798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022071.4. 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
	SH2D4A	NM_022071.4	MANE Select	c.787G>A	p.Gly263Arg	missense	Exon 7 of 10	NP_071354.2
	SH2D4A	NM_001174159.2		c.787G>A	p.Gly263Arg	missense	Exon 7 of 10	NP_001167630.1	Q9H788-1
	SH2D4A	NM_001363110.2		c.706G>A	p.Gly236Arg	missense	Exon 6 of 9	NP_001350039.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D4A	ENST00000265807.8	TSL:2 MANE Select	c.787G>A	p.Gly263Arg	missense	Exon 7 of 10	ENSP00000265807.3	Q9H788-1
	SH2D4A	ENST00000519207.5	TSL:1	c.787G>A	p.Gly263Arg	missense	Exon 7 of 10	ENSP00000428684.1	Q9H788-1
	SH2D4A	ENST00000962928.1		c.787G>A	p.Gly263Arg	missense	Exon 7 of 10	ENSP00000632987.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 251038 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461792 Hom.: 0 Cov.: 29 AF XY: 0.0000151 AC XY: 11 AN XY: 727198

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111946

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000475 Hom.: 0

Bravo AF: 0.0000340

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.39
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.28	N
PhyloP100		3.6
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.13
Sift	Benign	0.28	T
Sift4G	Benign	0.85	T
Polyphen		0.96	D
Vest4		0.30
MutPred		0.28		Gain of methylation at G263 (P = 0.016)
MVP		0.41
MPC		0.0054
ClinPred		0.21	T
GERP RS		3.0
Varity_R		0.040
gMVP		0.21
Mutation Taster		=95/5	polymorphism

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: rs201387983; hg19: chr8-19221663; COSMIC: COSV56122446; COSMIC: COSV56122446;