chr17-28661836-C-A

Variant names:

• chr17-28661836-C-A
• rs772080050
• NM_006923.4:c.41G>T

Variant summary

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

The NM_006923.4(SDF2):​c.41G>T​(p.Ser14Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S14N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDF2 NM_006923.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826
• Publications: 1 publications found

Genes affected

SDF2 (HGNC:10675): (stromal cell derived factor 2) The protein encoded by this gene is believed to be a secretory protein. It has regions of similarity to hydrophilic segments of yeast mannosyltransferases. Its expression is ubiquitous and the gene appears to be relatively conserved among mammals. Alternate splicing results in both coding and non-coding variants. A pseudogene of this gene is located on chromosome 15. [provided by RefSeq, Dec 2011]

SUPT6H (HGNC:11470): (SPT6 homolog, histone chaperone and transcription elongation factor) Enables histone binding activity. Involved in negative regulation of histone H3-K27 methylation and positive regulation of transcription elongation from RNA polymerase II promoter. Predicted to be located in nucleoplasm. Predicted to be part of transcription elongation factor complex. Predicted to be active in transcriptionally active chromatin. [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=0.11305565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006923.4. 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
	SDF2	NM_006923.4	MANE Select	c.41G>T	p.Ser14Ile	missense	Exon 1 of 3	NP_008854.2
	SDF2	NR_045585.2		n.149+210G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDF2	ENST00000247020.9	TSL:1 MANE Select	c.41G>T	p.Ser14Ile	missense	Exon 1 of 3	ENSP00000247020.3	Q99470
	SDF2	ENST00000585428.1	TSL:1	n.81G>T		non_coding_transcript_exon	Exon 1 of 2
	SDF2	ENST00000893452.1		c.41G>T	p.Ser14Ile	missense	Exon 1 of 4	ENSP00000563511.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.83
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.16
Sift	Uncertain	0.022	D
Sift4G	Benign	0.072	T
Polyphen		0.20	B
Vest4		0.20
MutPred		0.53		Gain of sheet (P = 0.0125)
MVP		0.23
MPC		0.53
ClinPred		0.55	D
GERP RS		2.5
PromoterAI		0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.51

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: rs772080050; hg19: chr17-26988854;