chr15-78092684-T-G

Position:

• chr15-78092684-T-G

Variant summary

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

The NM_001101404.2(SH2D7):​c.100T>G​(p.Phe34Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000278 in 1,439,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SH2D7 NM_001101404.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19

Genes affected

SH2D7 (HGNC:34549): (SH2 domain containing 7)

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/exons	MANE	Protein	UniProt
SH2D7	NM_001101404.2	c.100T>G	p.Phe34Val	missense_variant	1/6	ENST00000328828.6	NP_001094874.1
SH2D7	XM_047432942.1	c.-58T>G		5_prime_UTR_variant	1/7		XP_047288898.1
SH2D7	XM_017022487.2	c.66-1432T>G		intron_variant			XP_016877976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D7	ENST00000328828.6	c.100T>G	p.Phe34Val	missense_variant	1/6	5	NM_001101404.2	ENSP00000327846.5
SH2D7	ENST00000409568.6	c.-228-1432T>G		intron_variant		5		ENSP00000386676.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1439228 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 713672

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000503

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2022

The c.100T>G (p.F34V) alteration is located in exon 1 (coding exon 1) of the SH2D7 gene. This alteration results from a T to G substitution at nucleotide position 100, causing the phenylalanine (F) at amino acid position 34 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.24
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.46
MutPred		0.40		Gain of helix (P = 0.0854);
MVP		0.72
MPC		0.17
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.45
gMVP		0.72

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: chr15-78385026;